Salvia miltiorrhiza
1、 Pharmacopoeia standard of Salvia miltiorrhiza       This product is the dried roots and rhizomes of Salvia miltiorrhiza bge., a Labiatae plant. .
      [character] the rhizome of this product is short and thick, and sometimes the stem base remains at the top. The roots are several strips, long cylindrical, slightly curved, some branches with whisker like fine roots, 10 ~ 20cm long, 0.3 ~ 1cm in diameter. The surface is brownish red or dark brownish red, rough, with longitudinal wrinkles. The outer skin of the old root is loose, mostly purple brown, and often exfoliated in a scaly form. . It is slightly bitter and astringent.
      The cultivated product is thick, with a diameter of 0.5 ~ 1.5cm. The surface is reddish brown, with longitudinal wrinkles, and the skin is close and not easy to peel off. The texture is solid, the section is relatively flat, and it is slightly horny.
      [identification] (1) the powder of this product is reddish brown. The stone cells are round, triangular, rectangular or irregular, and also elongated in fiber shape, with uneven edges, 14-70 μ m in diameter and 257 μ m in length. The pore groove is obvious, and some cell cavities contain yellowish brown substances. Wood fibers are mostly fiber tracheids, long fusiform, with oblique sharp or blunt ends, 12-27 μ m in diameter, with marginal pits in the shape of dots, pits in the shape of oblique cracks or cross, and sparse pore grooves. The diameter of reticulate duct and marginal pit duct is 11 ～ 60 μ M.
      (2) . Another 1g of Salvia miltiorrhiza reference material was taken and prepared into the reference material solution by the same method. Then take tanshinone IIA reference substance and salvianolic acid B reference substance, add ethanol to make a mixed solution containing 0.5mg and 1.5mg per 1ml, respectively, as the reference solution. According to the test of thin-layer chromatography (general rule 0502), suck 5 μ l of each of the above three solutions, dot them on the same silica gel G thin-layer plate respectively, make them into strips, use chloroform toluene ethyl acetate methanol formic acid (6:4:8:1:4) as the developing agent, develop them to about 4cm, take out, dry them, and then use petroleum ether (60 ～ 90 ℃) - ethyl acetate (4:1) as the developing agent, develop them to about 8cm, take out, dry them, and view them under sunlight and ultraviolet light (365nm), respectively. In the chromatogram of the test sample, spots or fluorescent spots of the same color appear at the corresponding positions of the chromatogram of the control medicinal material and the chromatogram of the control sample.
      [check] moisture   .
      Total ash   Not more than 10.0% (general rule 2302).
      Acid insoluble ash   Not more than 3.0% (general rule 2302).
      Heavy metals and harmful elements   According to the determination method of lead, cadmium, arsenic, mercury and copper (general rule 2321 atomic absorption spectrophotometry or inductively coupled plasma mass spectrometry), lead shall not exceed 5mg/kg; Cadmium shall not exceed 0.3mg/kg; Arsenic shall not exceed 2mg/kg; Mercury shall not exceed 0.2mg/kg; .
      [extract] water soluble extract   It shall be determined according to the cold leaching method under the determination method of water-soluble extract (general rule 2201), and shall not be less than 35.0%.
      Alcohol soluble extract   According to the hot leaching method under the determination of alcohol soluble extract (general rule 2201), the use of ethanol as solvent shall not be less than 15.0%.
      [content determination] tanshinones   Determine according to high-performance liquid chromatography (general rule 0512).
      Chromatographic conditions and system suitability test   ; Acetonitrile was used as mobile phase a, and 0.02% phosphoric acid solution was used as mobile phase B. gradient elution was performed according to the following table; The column temperature was 20 ℃; .
    --------------------------------------------
      Time (min) mobile phase a (%)         Mobile phase B (%)
    --------------------------------------------
    0～6         61               39
    6～20                 61→90           39→10
    20～20.5     90→61           10→39
    20.5～25     61               39
    --------------------------------------------
      Preparation of reference solution   Take an appropriate amount of tanshinone IIA reference substance, accurately weigh it, put it into a brown measuring flask, add methanol to make a solution containing 20 μ g per 1ml.
      Preparation of test solution   Take about 0.3g of this product powder (passing through No. 3 screen), weigh it precisely, place it in a corked conical flask, add 50ml of methanol precisely, close the stopper, weigh it, sonicate (power 140W, frequency 42khz) for 30 minutes, cool it, weigh it again, make up the lost weight with methanol, shake it well, filter it, and take the filtrate.
      Assay   Accurately suck 10 μ l of the reference solution and 10 μ l of the test solution respectively, inject them into the liquid chromatograph, and determine. The relative retention time of cryptotanshinone and tanshinone Ⅰ was calculated with tanshinone Ⅱ a reference substance as reference and its corresponding peak as s peak. The relative retention time should be within ± 5% of the specified value. The relative retention time and correction factor are shown in the table below:
    ------------------------------------------
      Components (peaks) to be tested               Relative retention time         Correction factor
    ------------------------------------------
      Cryptotanshinone         0.75                        one point one eight
      Tanshinone ⅰ         0.79                        one point three one
      Danshen copper Ⅱ a      1.00                        one
    ------------------------------------------
      Taking the peak area of tanshinone Ⅱ a as the control, the contents of cryptotanshinone, tanshinone Ⅰ, tanshinone Ⅱ a were calculated by multiplying the correction factor respectively.
      The total amount of tanshinone Ⅱ a (c19h18o3), cryptotanshinone (c19h20o3) and tanshinone Ⅰ (c18h12o3) in this product shall not be less than 0.25% according to the dry product.
      Salvianolic acid b  Determine according to high-performance liquid chromatography (general rule 0512).
      Chromatographic conditions and system suitability test   ; The mobile phase was acetonitrile-0.1% phosphoric acid solution (22:78); The column temperature was 20 ℃; .
      Preparation of reference solution   Take an appropriate amount of salvianolic acid B reference substance, accurately weigh it, add methanol water (8:2) mixed solution to make a solution containing 0.10mg per 1ml.
      Preparation of test solution   Take about 0.15g of this product powder (passing through No. 3 screen), weigh it accurately, place it in a corked conical flask, add 50ml of methanol water (8:2) mixed solution precisely, close the stopper, weigh it, sonicate (power 140W, frequency 42khz) for 30 minutes, cool it, weigh it again, make up the lost weight with methanol water (8:2) mixed solution, shake it well, filter it, accurately measure 5ml of the continued filtrate, transfer it to a 10ml measuring flask, add methanol water (8:2) mixed solution to dilute to the scale, shake it well, filter it, and take the continued filtrate.
      The determination method is to precisely suck 10 μ l of the reference solution and 10 μ l of the test solution, inject them into the liquid chromatograph, and determine.
      According to the calculation of dry product, the content of salvianolic acid B (c36h30o16) shall not be less than 3.0%.
      Decoction pieces
      [processing] remove impurities and residual stems of Salvia miltiorrhiza, wash, moisten, cut thick pieces, and dry.
      This product is a thick round or oval shaped piece. The outer skin is brownish red or dark brownish red, rough, with longitudinal wrinkles. The cut surface is fissured or slightly flat and dense, some are horny, the skin is brownish red, the wood is grayish yellow or purplish brown, and has yellow white radial texture. It is slightly bitter and astringent.
      [inspection] acid insoluble ash   The same as medicinal materials, not more than 2.0% (general rule 2302).
      ; No less than 11.0% of the same medicinal materials.
      [identification], [inspection] (moisture and total ash content) [extract] (water-soluble extract) are the same as that of medicinal materials.
      ; Take Danshen Tablets and fry them dry according to the wine roasting method (general rule 0213).
      This product is shaped like Danshen tablets, with a reddish brown surface and a slight wine aroma.
      [check] moisture   For the same medicinal material, it shall not exceed 10.0% (the second method of general rule 0832).
      [extract] alcohol soluble extract is the same as that of medicinal materials, and shall not be less than 11.0%.
      [identification] [inspection] (total ash) [extract] (water-soluble extract) is the same as that of medicinal materials.
      [nature, taste and meridian tropism] bitter, slightly cold. Heart returning and liver meridian.
      [functions and indications] activating blood circulation and removing blood stasis, dredging meridians and relieving pain, clearing the heart and removing irritations, cooling blood and eliminating carbuncle. It is used for chest pain, abdominal flank pain, symptom accumulation, heat pain, restlessness, irregular menstruation, dysmenorrhea, amenorrhea, sore swelling and pain.
      [usage and dosage] 10 ～ 15g.
      [note] it should not be used with resveratrol.
      [storage] put it in a dry place.


2、 Chemical constituents of Salvia miltiorrhiza
1. among the fat soluble components, those with quinone and ketone structure include:Tanshinone Ⅰ、TanshinoneⅡA、TanshinoneⅡB[1，2]、TanshinoneⅤ、TanshinoneⅥ[2]，Cryptotanshinone（cryptotanshinone)[1]， Isotanshinone Ⅰ, Ⅱ [3], Ⅱ b[4], isocryptotanshinone [3], hydroxytanshinone IIA, methyltanshinate [1], Dan shexinkum a, B, c[1], d[6], dihydroisotanshinone Ⅰ [7], neocryptotanshinone [4], deoxyneocryptotanshinone shinone) [8], 2-isopropyl-8-methylphenanthrene-3,4-dione [9], nortanshinone, tanshindiol a, B, c[10], code named ro-090680,Tanshinone（miltirone）[11]， 1-hydroxytanshinone, 1-dihydrotanshinone iia[12], 1-hydroisocryptotanshinone [13], 3 α - hydroxytanshinone iia[10], 1,2-dihydrotanshinone [14], formyltanshinone, methylenedihydrotanshinone, 7 β - hydroxy-8,13-rosin diene-11, 12 Dione (7 β -hydroxy-8-13-abietadiene-11, 12 Dione), 1,2,5,6-tetrahydrotanshinone (1,2,5,6-tetcmlibahydrotanshinone) Ⅰ, 4-methylenemiltiorone [15], tanshinlactone [17], dihydrotanshinlactone [18], Danshen spiroketalactone, epidanshenspiroketalone AC tone) [19], Salvia miltiorrhiza spironolactone II [18], They are cryptoac etalide [20] and salvianone [22]. ; Other types of structures are: norsalvioxide [22],Mirrorsonol（ferruginol)[12]，Salvianol（salviol)[14]， Sugiol [15] et al. Water soluble phenolic acid compounds include: salvianic acid A, B, C,Tanshinic acid Aalso calledDanshensu, whose structure is d (+) - β - (3,4-dihydroxyphenyl) lactic acid [d (+) - β - (3,4-dihydroxyphenyl) lactic acid], tanshinic acid B is formed by condensation of 3 molecules of tanshinol and 1 molecule of caffeicacid, which isSalvianolic acid B; tanshinic acid C is a condensate of 2 molecules of tanshinol [24, 25];Salvianolicacid a、salvianolic acid B、salvianolic acid C、salvianolic acid D、salvianolic acid E、salvianolic acid G[26-29]；Rosmarinic acid（rosmarinicacid)，methyl rosmarinate （methylrosmarinate)[27]， Monomethyl shikonate, dimethyl shikonate, ethyl shikonate [30], lithospermicid b[31],Protocatechuic aldehyde（protocaterchualdehyde)，caffeic acid[27]，Isoferulic acid(isoferulicacid) [30] et al. Also containsBaicalin（baicalin)[32]，Isoimperatoride（isomperatorin)[13]，Ursolic acid（ursolicacid)，β - sitosterol（β-stiosterol)，Carotene（daucosterol)[35]， 5- (3-hydroxypropyl) - 7-methoxy-2 - (3-methoxy-4-hydroxyphenyl) - 3-benzofuranal [5 (3-hydroxypropyl) - 7-methoxy-2 - (3-methoxy-4-hydroxyphenyl) - 3-benzofurancarbaldehyde][33], Tigo Genin [1],Stigmasterol(stigmasterol) [7] et al.

Share in RhizomeTanshinone Ⅰ、TanshinoneⅡA，TanshinoneⅡB，Cryptotanshinone, tanshinone B,Dihydrotanshinone Ⅰ, methylene tanshinone [34].

From Danshen InjectionTanshinone Ⅰ, cryptotanshinone, isoferulic acid, protocatechuic acid, succinic acid, rosmarinic acid, salvianolic acid a[35].

2. Ganxi Sargassum root containsTanshinone Ⅰ、TanshinoneⅡA[36]，TanshinoneⅡB[37]，Cryptotanshinone, hydroxytanshinone, methyl tanshinate [36], prgewaqinone A and B, methylene tanshinone, 1,2-dihydrotanshinone [38],oleanolic acid （oleanolicacid)， Przewanoicacid a, b[39], tanshinone B, tanshinone, nortanshinone,Dihydrotanshinone Ⅰ[40], przewalskin [37], przewalskenicacid a[41], przewalskinone, 1,5-hydroxy-3-methylanthraquinone [42],β - sitosterol[36]。

In addition, the same plant ① Salvia miltiorrhiza Bunge root contains:Tanshinone Ⅰ、TanshinoneⅡA，Dihydrotanshinone Ⅰ, dihydroisotanshinone Ⅰ, tanshinone, hydroxytanshinone IIA, methylene tanshinone, methyl tanshinate, tanshinone B, tanshinone, nortanshinone, Ro-099680， 1, 2, 15, 16 tetrahydrotanshinone (1, 2, 15, 16 tetcmlibahydrotanshi quinone), tanshinaldehyde [43]. ② The root of pseudo Salvia miltiorrhiza contains diterpenoid compounds: tanshinaldehyde [44], triterpenoid compounds: 2 α. 3β， 24-trihydroxy-ursol-12-en-28-carboxylic acid (2 α, 3 β, 24-hydroxyurs-12-en-oic acid), 2 α, 3 α, 24-trihydroxyursol-12-en-28-carboxylic acid (2 α, 3 α, 24-tcmlibihydroxyurs-12-en-28-oic acid), 2 α, 3 α - dihydroxyursol-28-carboxylic acid (2 α, 3 α - dihydroxyurs-12-en-28-oic acid), 2 α, 3 β - dihydroxyursol-12-en-28-oic acid (2 α, 3 β - dihydroxyursol-28-oic acid 3 β - dihydroxyurs-12-en-28-oic acid), 2 α, 3 α, 19 trihydroxyursolic acids (2 α, 3 α, 19-TCMLIBihydroxyurs-12-en-28-oicacid)，2α，3β， 2 α -3 β, 19-tcmlibihydroxyurs-12-en-28-oic acid), 3-o-acetyloleanolic acid [45]

3、 Pharmacological effects of Salvia miltiorrhiza
1. effects on cardiovascular system: 1.1. seven dogs weighing 13.5-18kg were anesthetized intravenously with sodium pentobarbital 30mg/kg. According to Fick's principle, the cardiac output was calculated from the oxygen consumption per minute and the difference of arterial and venous blood oxygen content, and the values were calculated. . The control test was performed once before administration, and then the dose of sodium tanshinone Ⅱ -a sulfonate was 20mg/kg by intravenous injection, the concentration of the drug solution was 10mg per LML, the flow rate was 2ml per minute, and the test was performed once 1 / 2 and 1 hour after administration. See Table 9 for the average values of the results of the 7 dogs. Thirty minutes after intravenous injection of sodium tanshinone Ⅱ a sulfonate, the mean femoral artery pressure increased slightly, and the cardiac index and left ventricular work volume increased compared with those before administration (p< 0.05). Heart rate and external vascular resistance were not significantly changed.

The above results indicate that the cardiac output and left ventricular work volume with mild blood pressure increase slightly after an intravenous bolus injection in anesthetized dogs. Another experiment proved that sodium tanshinone Ⅱ a sulfonate did not significantly change the femoral artery blood pressure of dogs with ligation of the anterior descending artery. However, within 30 minutes after 2mg/kg injection, the left ventricular pressure gradually changed significantly. Although the left ventricular peak pressure was reversed from the decreased value in the control group to increased, there was no significant difference compared with the control group. The left ventricular end diastolic pressure increased in the control group, while it decreased slightly in this group, P< 0.01.

1.2. effect of Danshensu on isolated porcine coronary artery: the isolated coronary artery was prepared by constant velocity perfusion of the improved oglatcmlibee et al. Different from the former, both ends of the isolated porcine coronary artery segment were ligated on the perfusion preparation cannula. The experiment is divided into: 1.2.1. effect of Danshensu on morphine contraction of coronary artery: the same specimen was given three successive increasing doses of morphine hydrochloride, and the maximum value of △ P after each administration was recorded. The perfusion system was rinsed with Krebs henselait solution for three times. After the baseline returned to normal, Danshensu (making the drug concentration in the perfusion system 1x10 (-6) g/ml) was given, and the effect was obvious, morphine hydrochloride of the same three doses was given repeatedly.

1.2.2. effect of tanshinol on propranolol contraction of coronary artery: the administration procedure is the same as that in 1. After the above doses of tanshinol are used, four increasing doses of propranolol hydrochloride are given repeatedly.

1.2.3. after tanshinol administration, repeat the administration of three increasing doses of KCl.

1.2.4.3 increasing doses of reserpine. Each specimen was given KCl at the end of the experiment, and those that did not contract were removed.

31 samples of Danshensu were used for 40 experiments, △ p-2.54 ± 0.48mmhg (p< 0.001), and the normal perfusion pressure was 82.34 ± 1.08mmhg, showing significant coronary artery dilatation. Danshensu antagonized the coronary artery contraction of morphine and propranolol.

Danshensu could antagonize the isolated coronary artery contraction induced by propranolol, but could not antagonize the coronary artery effect caused by depolarization of high K +, suggesting that it may be beneficial to antagonize the potential coronary artery contraction effect of Danshensu while using morphine for analgesia in acute myocardial infarction.

In addition, the experiment also proved that other components of Salvia miltiorrhiza, such as sodium tanshinone Ⅱ -a sulfonate (Ds-201), Salvia miltiorrhiza diterpenoid acid mixture (ds-781) and Protocatechualdehyde, could significantly constrict porcine coronary arteries.

1.3. effect of Salvia miltiorrhiza on left ventricular diastolic function in dogs with coronary artery stenosis: experimental animals weighing 14-20kg dogs, either male or female. Sodium pentobarbital was anesthetized intravenously (30mg/kg), and the trachea was cut open for positive pressure artificial respiration. Cut 1-rib at the left edge of sternum to expose the heart. . The critical stenosis is based on relaxing the coronary artery after blocking the coronary blood flow for 15 seconds, and the reactive congestion just disappears, so that the coronary cross-sectional area is reduced by 87%. The average arterial pressure (PA) is measured by the femoral artery cannula and the aorta. Catheters were inserted in the less vascular area of the apex, and the indoor pressure was measured with stathamp50 pressure transducer. .

The animals were divided into 3 groups with 8 animals in each group. ; Group II: Salvia miltiorrhiza group, after 15 minutes of coronary stenosis, the left atrium was cannulated and injected with 0.15g/kg Salvia miltiorrhiza injection (Salvia miltiorrhiza injection was produced by Shanghai first pharmaceutical factory, 2ml per ampoule, containing 3G crude Salvia miltiorrhiza medicine); Group Ⅲ; In glucose group, 15 minutes after coronary artery stenosis, 5% glucose solution equal to Salvia miltiorrhiza injection was injected into the left atrium to observe the changes of left ventricular diastolic function after administration. The experimental results showed that after using Salvia miltiorrhiza, the -dp/dtmax and -vcet values were improved, indicating that Salvia miltiorrhiza can increase the rate of decline of indoor pressure, increase the ventricular active filling and ventricular compliance, so that the ventricle can accept more blood at the same filling pressure, improve the cardiac diastolic function, and improve the cardiac systolic function through Starling's law. It is worth noting that Danshen injection can significantly increase the coronary flow during coronary stenosis, and CBF increases significantly immediately after administration in the left atrium, reaching the highest value at 30 minutes after injection, while the diastolic indexes such as: -dp/atmax, VCE, and T values significantly improved after CBF changes, and HR and PA did not change significantly during the whole experimental process, so it is suggested that the improvement of Danshen on diastolic function is achieved by increasing CBF.

1.4. protective effect of Salvia miltiorrhiza on myocardial ischemia and reperfusion: first perform 20 minutes of control perfusion, and then cause isolated heart ischemia for 30 minutes with or without Salvia miltiorrhiza, and then repeat perfusion for 30 minutes. The results showed that after adding Salvia miltiorrhiza in the perfusate, the left ventricular diastolic pressure suddenly increased, and then gradually decreased to 3.5% of the control value before treatment. During reperfusion after myocardial ischemia, the recovery of left ventricular diastolic pressure in the heart treated with Salvia miltiorrhiza was significantly better than that in the untreated heart (p< 0.01), and the degree of myocardial contraction indicated by the increase of left ventricular end diastolic pressure was also significantly lower than that in the untreated heart (p< 0.01). . At the same time, myocardial contraction becomes more stable. Salvia miltiorrhiza could attenuate myocardial contractility (the left ventricular diastolic pressure of the heart without Salvia miltiorrhiza treatment was 108.3 ± 9.4cmh2o, while that of the heart treated with Salvia miltiorrhiza was 39.1 ± 7.9cmh2o), accompanied by an increase in coronary blood flow (from 12.4 ± 1.2ml/ min to 18.3 ± 3.4ml/ min) and left ventricular end diastolic pressure (from 6.0 ± 3.1cmh2o to 12.3 ± 4.0cmh2o). Although the coronary blood flow rate was higher in the salvia miltiorrhiza treated group after reperfusion, there was no significant difference between the two groups compared with the untreated group.

Another group of experiments observed the washing rate of Salvia miltiorrhiza to determine whether the results of reperfusion were affected by residual Salvia miltiorrhiza. For this purpose, the heart was perfused with perfusion solution without Salvia miltiorrhiza for 15 minutes and then with Salvia miltiorrhiza for 5 minutes. Finally, the perfusate was used for another 20 minutes and 20 minutes. The results showed that after 5 minutes of perfusion with Salvia miltiorrhiza, the left ventricular diastolic pressure of rats rapidly returned to the level before perfusion. However, within 20 minutes without Salvia miltiorrhiza perfusion, the recovery of coronary blood flow rate was much slower. Compared with the first 15 minutes of control perfusion, the left ventricular diastolic pressure decreased significantly only in the first 5 minutes of Salvia miltiorrhiza perfusion, while during this period, the coronary blood flow increased significantly. . This result indicates that Salvia miltiorrhiza has a protective effect on the heart after myocardial ischemia and reperfusion.

1.5. effect of water-soluble components of Salvia miltiorrhiza on acute myocardial infarction in dogs: 57 mongrel dogs, weighing 12-26kg, male, were made into acute myocardial infarction model. After sodium pentobarbital anesthesia, the left chest was opened, and the midpoint of the left anterior descending coronary artery (LAD) and the root of the largest oblique branch artery were ligated (short for blocking LAD). Cause a relatively constant ischemic area of the left ventricle. Recorded indicators: record LVPSP and LVEDd through apical intubation; ; The femoral artery pressure (MBP) was recorded. The above indicators were recorded every 5 minutes before and after lad blockade, and the chest wall was sutured until 30 minutes after lad blockade. After 24 hours, the myocardial infarction scope (MIS) was quantitatively determined by nitrotetrazolium blue (n-bt) staining method. The constant experimental conditions were: lidocaine (8mg/kg) was injected intravenously before blocking lad.

The experiment was randomly divided into 6 groups: 1. The control group, 14 dogs, did not give treatment drugs after blocking lad; 2. In the Danshensu ds-182 group, 11 dogs were intravenously injected with ds-1828mg/kg after blocking lad; 3. ; 4. Protocatechualdehyde PCAD group, 5 dogs, after blocking lad, PCAD 8mg/kg was slowly injected intravenously; 5. In the dipyridamole group, 12 dogs were intravenously injected with dipyridamole 1mg/kg slowly after blocking lad; 6. In dopamine group, 4 dogs were intravenously injected with 0.4mg/kg dohexylamine after lad blockade. The experimental results showed that blocking the blood flow of the anterior descending branch of the left coronary artery caused a significant increase in heart rate, a mild decrease in mean blood pressure, a significant decrease in systolic blood pressure in the left ventricle and a significant increase in end diastolic pressure. Danshensu (ds-182), Salvia miltiorrhiza terpenoid acid mixture (ds-781) and protocatechuaquinone (PCAD) had slight effects on the changes of heart rate and MBP after blocking lad, and there was no significant difference between the two groups. However, in this group, the heart rate of ds-182 group was significantly faster than that before myocardial infarction at 15 and 30 minutes (P < 0.05), and the rest were not significantly increased or decreased. Ds-182 can also increase the average value of LVPSP. LVEDP turned upward to downward, suggesting that ds-182 can improve left ventricular function. In ds-781 group and PCAD group, LVPSP was negative, and the decrease value of LVPSP was greater in PCAD group; For LVEDP, ds-781 significantly decreased it, while PCAD significantly increased it, indicating that these two components of Salvia miltiorrhiza are detrimental to left ventricular systolic function. The weight of myocardial ischemic area and MIS measurement of dogs in each group showed that ds-182 and dipyridamole groups were similar, and the curative effect of ds-781 group was about 62.7% of ds-182, while PCAD had a weak effect on reducing MIS. The mechanism of ds-182 against myocardial ischemia may be related to the relaxation of coronary artery and the anti aggregation of small blood poles.

1.6. effect of sodium tanshinone Ⅱ a sulfonate on the range of myocardial infarction in dogs with myocardial infarction: the dogs were randomly divided into three groups: 1. The control group of myocardial infarction, 10 dogs, could not receive any drug treatment after ligation of the anterior descending branch; 2. In the sodium tanshinone IIA sulfonate treatment group, 10 dogs were intravenously injected with 2mg/kg sodium tanshinone ia sulfonate (semi synthetic by Shanghai Institute of Materia Medica) from the time of ligation of the anterior descending branch, and then injected once every 4 hours for a total of 4 times. 3. . (p< The effect on heart rate, blood pressure and myocardial oxygen consumption index was not obvious. In addition, the weight of ischemic area in the control group was 15.20 ± 5.20g, and the range of myocardial infarction accounted for 20.8 ± 1.44% of the left ventricle. The weight of ischemic area in the sodium tanshinone Ⅱ a sulfonate treatment group was 3.00 ± 0.70g, and the range of myocardial infarction was reduced to 5.00 ± 1.30%. These two indicators were very significant compared with the control group (p< 0.001); The effect of propranolol was more obvious. The ischemic area weighed only 0.40 ± 0.20g, and the range of myocardial infarction was 0.63 ± 0.31% (p< 0.001). Huguojun et al also confirmed this result, but it is different from that 1V can reduce the elevation of S-T segment.

1.7. effect of Salvia miltiorrhiza on pulmonary artery pressure in rabbits: ten rabbits, half male and half female, weighing 2.3-3.0kg, were injected with 25% urethane via ear vein, anesthetized with 1.2g/kg urethane, injected with 1000u/kg heparin via femoral artery, sweated chest from 2-4 ribs at the left edge of sternum, exposed pulmonary artery, cut open center bag, and directly inserted needle head into pulmonary artery trunk in mediastinum to record pulmonary artery blood pressure. . Use Salvia miltiorrhiza injection (LML containing 1.5g Salvia miltiorrhiza) 3g/kg and slowly inject it from the infusion tube at a constant speed within 2 minutes. Before injection of Salvia miltiorrhiza, the same amount of equal pH niuli saline was injected to act as self control. When all indicators are stable, the formal experiment is started. Each index was recorded synchronously every 5 minutes, and the average value of 4 times was taken as the pre experiment control. . PAP and other indicators were recorded once at 1, 2, 3, 4, 7, 9, 11, 15 and 20 minutes before the injection of normal saline and Salvia miltiorrhiza. The experimental results were tested by analysis of variance.

The results showed that anesthesia was free from intravenous injection of Salvia miltiorrhiza. It can make the femoral artery blood pressure drop temporarily, and significantly reduce the systolic and diastolic blood pressure of pulmonary artery, with the largest drop in 3 minutes after injection, and it has been close to the control value by 40 minutes. The above effects may be related to the selective relaxation effect of Salvia miltiorrhiza on pulmonary arteriolar smooth muscle, or it may open the pulmonary capillary network and accelerate the flow rate of microvessels.

Qiyouling et al reported that Salvia miltiorrhiza had no significant effect on normal pulmonary artery pressure and femoral artery pressure in anesthetized dogs, and seemed to have a certain antihypertensive effect on pulmonary and femoral hypertension induced by norepinephrine, but there was no significant difference after statistical treatment. However, the statistical results of the duration of pulmonary hypertension showed that Salvia miltiorrhiza can significantly shorten the duration of pulmonary hypertension induced by norepinephrine, which may be caused by affecting A-receptor mechanism.

1.8. protective effect of sodium tanshinone Ⅱ a sulfonate on myocardial calcium abnormality in guinea pigs: healthy guinea pigs, weighing 250-280g, fasting overnight before the experiment, weighing, heparin 5mg intraperitoneal injection, pentobarbital sodium 30mg/kg intraperitoneal injection 20 minutes later. After anesthesia, the chest was opened, and the heart was quickly removed and immersed in ice cooled k-solution. After aortic intubation, the heart was placed into a constant temperature and pressure isolated heart perfusion device. At 37 ℃, 80cmh2o pressure, the heart was perfused by langenclorff method. The calcium anomaly model was created according to the requirements of document 53, and then the experiment was carried out.

The results showed that sodium tanshinone Ⅱ a sulfonate had obvious protective effect on myocardial calcium paradoxical injury, inhibited calcium influx, and alleviated calcium deposition in central tissue and protein (enzyme) release caused by myocardial injury during calcium paradoxical process (p< 0.01). This effect has a dose-dependent relationship within a certain range. 30mg/l and 40mg/l could reduce the protein release of myocardial tissue by 52.8% and 66.2%, respectively, and reduce the calcium uptake by 25.8% and 36.9%. The effect is better than that of verapamil. Because the large amount of calcium influx in calcium anomaly is initiated by lipid peroxidation reaction caused by oxygen free radicals on the basis of enhanced membrane permeability caused by calcium free perfusion, it is presumed that sodium tanshinone IIA sulfonate may inhibit calcium influx through membrane stabilization and oxygen free radical scavenger effect.

1.9. effect of sodium tanshinone Ⅱ a sulfonate on slow response action potential of single cells in guinea pig ventricular myocytes the isolation method of calcium tolerant adult guinea pig ventricular myocytes is as reported and slightly modified. Isolated adult guinea pig ventricular myocytes were partially depolarized in high potassium (25mmol/l) solution to inactivate sodium channels, and slow response action potentials were evoked by intracellular stimulation. . In the concentration range of 20mmol/l, sodium tanshinone Ⅱ a sulfonate had a concentration dependent inhibitory effect on the slow response action potential enhanced by 0.28mmol/l isoproterenol. Moreover, the inhibitory effect was more obvious with the increase of isoproterenol concentration (69mmol/l-55mmol/l). These results suggest that sodium tanshinone Ⅱ a sulfonate may be a calcium antagonist.

In addition, 50-100mmol/l sodium tanshinone Ⅱ a sulfonate reduced the amplitude of fast response action potential of isolated adult guinea pig ventricular myocytes and prolonged the time to peak. It is suggested that high concentration of sodium tanshinone Ⅱ a sulfonate also has a certain blocking effect on sodium channels.

1.10. effects of sodium tanshinone Ⅱ a sulfonate on the electrical and mechanical activities of animal myocardium: guinea pigs and rabbits were killed. After dizziness caused by head strike, the hearts were taken and placed in 35 ± 1 ℃ physiological solution. After draining the blood stasis, the specimens of atrial or ventricular muscle strips or sinus node were prepared. The pig was stunned by electric shock. The heart was removed and placed in 35 ± 1 ℃ physiological solution for several minutes. After draining the blood stasis, it was stored in 4-8 ℃ physiological solution. The right ventricular meat column was removed at room temperature and completed within 1 hour. . In vitro myocardial experiments in guinea pigs, rabbits and pigs showed that sodium tanshinone Ⅱ a sulfonate could inhibit myocardial contractility; The duration of action potential was shortened, but the L rate on o phase was less affected; Reduce the depolarization rate of slow reaction potential; Slow down the self-regulation of sinoatrial node cells. It is suggested that sodium tanshinone Ⅱ a sulfonate may affect the influx of Ca2 + into cells. In addition, the experimental results also showed that the concentration of sodium tanshinone Ⅱ a sulfonate that significantly inhibited muscle tone (4ug/ml) was less than the concentration that significantly affected action potential (40ug/ml).

Wenyunmang and others used rats aged 35 months and weighing 300-500g to inhibit vsmca2+ influx. . The above results suggest that at the cellular level, ca2+ plays an important role in the pathogenesis of genetic or secondary hypertension in rats, and Salvia miltiorrhiza can correct the abnormal vsmca2+ influx.

Sodium tanshinone Ⅱ a sulfonate can increase coronary blood flow, dilate microvessels, slow down heart rate and negative muscle strength. It has the common action characteristics of calcium antagonists. Experiments support that sodium tanshinone Ⅱ a sulfonate belongs to calcium antagonists. .

2. protective effect on myocardial ischemia and hypoxia: 2.1. hypoxia tolerance: 2.1.1. effect of Danshensu (B-3, 4-dihydroxyphenyllactic acid, ds-182) and two other water-soluble components on hypoxia tolerance time of mice: 70 mice, weighing 18-22g, were subjected to atmospheric pressure oxygen tolerance test in closed wide mouth bottles, and were administered after 20 minutes of intraperitoneal injection according to the literature method. They were randomly divided into 10 groups: control group, 10 rats, each of which was injected with 0.2ml of normal saline; ds-182a group, 15 rats, with a dose of 300mg / kg; ds-182a group, 15 rats, with a dose of; Ds-182b group, 15 rats, dose 450mg/kg; PCAD (protocatechuic aldehyde) group, 10 rats, the dose was 300mg/kg; ; In chlorpromazine group, 10 rats were injected with chlorpromazine 1mg/kg.

The experimental results showed that both doses of Danshensu (ds-182) could significantly prolong the hypoxia tolerance time of mice. The survival time of the control group was 18.4 ± 0.96 minutes, and that of ds-182 group was 28.93 ± 2.26 and 33.14 ± 2.40 minutes, respectively (p< o.01). Sodium tanshinone Ⅱ a sulfonate (Ds-201) was also prolonged to 23.7 ± 1.49 (p< 0.o5). Protocatechualdehyde (PCAD) is ineffective in anti hypoxia.

2.1.2. effect of sodium tanshinone IIA sulfonate on normobaric hypoxia in mice: the experiment was divided into control and administration groups, with 12 mice in each group. The mice were injected with sodium tanshinone IIA sulfonate by intraperitoneal injection. 1 / 2 or 1 hour after administration, the mice were put into a ground glass bottle with a volume of 150ml, and a little sodium lime was put into the bottle to absorb CO2 and water vapor. One mouse per bottle was sealed and sealed tightly after being put in, and the survival time was recorded. The significance of the mean difference between the groups was compared by time test. . The dose was 200mg/kg, a total of four batches were tested, and the average survival time was significantly longer than that of the control group (p< o.05-0.01).

2.1.3. effect of sodium tanshinone Ⅱ a sulfonate on lactic acid content in tissues of mice under atmospheric pressure and oxygen tolerance: 36 male mice were divided into three groups. Hypoxia group: mice were put into an oxygen consumption bottle. When the oxygen content in the bottle reached 6% (severe hypoxia), they were immediately put into an ice thermos bottle. After removal, the heart and brain were removed, weighed, and then ground into homogenate. 10% trichloroacetic acid precipitated protein, and lactic acid was determined according to the colorimetric method. . In each experiment, normal mice were used as controls to measure the lactic acid in tissues. The results showed that the content of lactic acid in the heart and brain of the hypoxia group was significantly increased compared with that of the normal group, while the content of lactic acid in the tissue did not increase after the hypoxia test with sodium tanshinone Ⅱ a sulfonate, which was similar to that of the normal group. The results showed that the degree of hypoxia was gradually deepened in mice, and the lactic acid content in heart and brain tissue was significantly increased, while sodium tanshinone Ⅱ a sulfonate could improve the disorder of myocardial metabolism caused by hypoxia. It is suggested that sodium tanshinone Ⅱ a sulfonate improves hypoxia tolerance in mice and is related to the improvement of myocardial metabolic disorder after hypoxia.

2.2. protective effect on myocardium: 2.2.1. ten male mice weighing 19-26g were used in the experiment. Divided into 2 groups. ; The other 5 mice were injected with normal saline as the control group. Five pairs of animals with similar body weight were selected from the two groups, and the animals in the two groups were placed in the water in the closed container for swimming for 31-36 minutes about 30 minutes after injection, and then the hearts were sacrificed after being removed from the container, and the ultrastructure was observed.

The above results showed that the change characteristics of hypoxia control group were consistent with the myocardial ultrastructural changes of acute hypoxia, and Salvia miltiorrhiza could alleviate the myocardial injury caused by hypoxia, which was consistent with the above experimental results.

2.2.2. effect of Salvia miltiorrhiza on preventing acute ischemic myocardial disc injury: rabbits were anesthetized with sodium pentobarbital, and the thorax was cut from the fourth, fifth, or fifth, sixth intercostal space of the left chest under disinfection conditions to expose the heart, and at the same time, artificial respirators were used to maintain animal respiration. The left anterior descending coronary vein was ligated. At about 5mm away from the root of the vein, some tissues surrounding the blood vessel and its surroundings were ligated twice with sutures. . In the limb lead recording after ligation, T-wave decline or ST segment elevation can occur. These changes were often seen in only one or two limb leads, and usually recovered within 24 minutes after ligation. All rabbits were intramuscularly injected with penicillin K or penicillin G 2million units after surgery. A part of rabbits were intravenously injected with saline as control. The injection time was, 4, 12, 20, 28, 36 and 44 minutes after ligation. The parameters of Danshen injection for the first time were about 0.5ml/kg (each LML was equivalent to 2G of crude drug) body weight, and then about 1.5ml/kg body weight for each injection. Forty eight minutes after ligation of the blood vessels, the animals were again thoracotomized under sodium pentobarbital anesthesia. A small piece of myocardium was taken from the heart ligation along the blood vessels at 1, 5, 9 and 13mm away from the ligation point. After sectioning, electron microscopy was performed. Results there was no significant difference in the degree of myocardial mitochondrial damage between the salvia miltiorrhiza group and the control group. However, piles of mitochondria were commonly found in the myocardial sections of the salvia miltiorrhiza group, which was less common in the control group. When the mitochondria in the ischemic myocardial tissue were significantly damaged, the discs of the control group were severely damaged, and some were in a paste shape; In the salvia miltiorrhiza group, the discs were mildly damaged, showing a small river shape, and a considerable number of discs were basically normal. It has been confirmed that there were some special areas in the discs, such as fasciaadthereus. Desmosome and nexus are related to the outward transmission of contractile tension of cardiomyocytes, the maintenance of cell contour and the transmission of excitation between cells, respectively. Salvia miltiorrhiza can reduce the damage of intervertebral disc and maintain the integrity of cell membrane, which may be a mechanism of its efficacy.

. Objective to explore the protective effect of Salvia miltiorrhiza on myocardium. The experimental results showed that when the left ventricular branch of coronary artery was ligated for 40 minutes, the content of myocardial lipid peroxide in ischemic area was positively correlated with the degree of ST segment elevation in ECG (r = 0.822, p< 02), and reduced the degree of ST segment elevation of ECG by 44.8-47.0% (p< 0.05) from 2 to 5 minutes after ligation of left ventricular branch of coronary artery. It is believed that the antioxidant effect of Salvia miltiorrhiza in vivo ischemia model can reduce membrane damage and block calcium influx, which is an important mechanism to protect myocardium and reduce abnormal electrical activity.

2.2.4. effect of sodium tanshinone IIA iodate on cardiac contraction amplitude of guinea pigs and rats: guinea pigs weighed 250-400g, isolated hearts were prepared according to Langendorf's method, and perfused with Tai's solution. . The drug concentrations in the perfusate were 0.5, 1, 10, and 20ug/ml, respectively. Each concentration was perfused for 20 minutes, and the contraction amplitude before and after treatment was recorded. Sodium tanshinone Ⅱ a sulfonate (0.5-20ug/ml) gradually aggravated the inhibition of myocardial contractility. After 10 minutes of perfusion, the contraction amplitude of the four concentrations decreased by 10%, 17%, 16% and 30%, respectively, which was significantly different from that of the control group. After 20 minutes of perfusion, the concentration of 0.5 and 1ug/ml decreased the contraction amplitude by 18 and 43%, respectively, compared with the control group, P< 0.01. Another group of 12 rats weighing 200-300g were anesthetized by intraperitoneal injection of 40mg/kg sodium pentobarbital; In group 2, 9 rats were anesthetized with ether, and then paralyzed with curcumine 4 or 5mg/kg intravenously. After endotracheal intubation, the chest cavity was cut under artificial respiration, and the stainless steel small hook was used to hold the apex of the heart, connect to the lever, record the heart contraction, and separate the heart and lung with plexiglass sheets to reduce the mechanical interference of breathing. After the heart rate and contractility were stable, normal saline was injected intravenously as control for 15 minutes. There was no change in heart rate and contractile amplitude. After injection of sodium tanshinone Ⅱ a sulfonate 0mg/kg for 2-3 minutes, the heart rate did not change significantly, and the contractile amplitude increased from 14 ± 8mm (mean ± standard deviation, the same below) to 17 ± 8mm (individual comparison p< 01), and the amplitude increase could be maintained for at least 10 min.

2.2.5. effect of sodium tanshinone Ⅱ a iodate on contraction of rabbit ventricular papillary muscle under hypoxia: take a rabbit weighing about 2kg, hit the head to make it comatose, take out the heart, cut off the left ventricular papillary muscle in Taiwan's solution, fix one end in the muscle groove, and connect the other end to the transducer to record isotonic contraction. The tais solution soaked in muscle was saturated with O2 at 32 ℃. After 30 min of equilibration, rectangular pulse stimulation (duration of about 5 ms, frequency of 12 times / min) was applied through a pair of electrodes made of acupuncture needles, and the stimulation intensity was about 10% higher than the threshold. . The results showed that sodium tanshinone Ⅱ a sulfonate significantly affected the rate of contraction amplitude reduction of rabbit ventricular papillary muscle under hypoxia. In the control group, the 7 papillary muscles were first equilibrated in Taishi solution with O2 for 60 minutes, and then moved into Taishi solution without O2. Under electrical stimulation, the time for the contraction amplitude to decrease by half was 4.6 ± 1.9 minutes. In the administration group, 7 papillary muscles were first equilibrated in O2 Taishi solution for 30 minutes. After 30 minutes of equilibration in the O2 tertile solution containing 100ug/ml of drug, and then transferred into the O2 free tertile solution containing the same concentration of drug, under the same electrical stimulation condition, the time for the contraction amplitude to decrease by half was 6.8 ± 1.8 minutes, which was significantly longer than that of the control group (p< 0.05).

2.2.6. effect of sodium tanshinone IIA sulfonate on coronary collateral circulation in dogs with myocardial infarction: 22 mongrel dogs weighing 11-16kg were used. They were anesthetized with 25mg/kg sodium pentobarbital intravenously. The left anterior descending coronary artery (LAD) and all its branches were exposed through thoracotomy from the left side. Lad was ligated and blocked. The changes of collateral circulation after myocardial infarction were observed by coronary artery tree casting method. The experimental results showed that the elevation of epicardial S-T segment in the sodium tanshinone IIA sulfonate group was significantly less than that in the control group. The coronary vascular tree disappeared or significantly narrowed in the 5-hour coronary vascular tree. Bridge collateral anastomotic vessels opened between the ischemic and non ischemic arteries. It is suggested that the mechanism of sodium tanshinone Ⅱ a sulfonate against myocardial ischemia is mainly related to opening the bridge collateral anastomoses between coronary arteries and increasing the blood perfusion in the ischemic area.

2.2.7. preventive and therapeutic effects of Salvia miltiorrhiza water extract on isoproterenol induced ventricular fibrillation in rats: Sprague Dawley, male. Isoproterenol (ISO) is a kind of drug used in the animal model of experimental ventricular fibrillation.

The experiment was divided into two parts: prevention and treatment. The prevention experiment was divided into two groups: group A was further divided into 525 ± 21g group (A1 group) and 387 ± 11g group (A2 group). Animals in group A1 were intraperitoneally injected with sodium pentobarbital (30mg/kg) and divided into three groups as follows: (1) Danshen group: animals were intraperitoneally injected with Danshen aqueous extract (sm-h); (2) Propranolol group: animals were intraperitoneally injected with propranolol aqueous solution; (3) Control group: animals were intraperitoneally injected with normal saline (A2 group animals were only divided into Salvia miltiorrhiza group and control group). Animals in each group were subcutaneously injected with ISO 30 minutes after injection of different solutions, and ECG was measured at different times.

The animals in group B were first lightly anesthetized with diethyl ether, and then their limbs were connected with ECG leads. The experiment was carried out 30 minutes after the animals were awake: (1) sm-h was injected intraperitoneally in Salvia miltiorrhiza group; (2) The control group was intraperitoneally injected with normal saline. The experimental method and process were the same as those of group A. The animals in the treatment experiment (520 ± 19g) were subcutaneously injected with ISO (1mg/kg) after intraperitoneal injection of normal saline for 30 minutes. When ventricular fibrillation (VF) occurred, sm-h was slowly injected from the femoral vein immediately. The fibrillation dose of ISO subcutaneously injected was lmg/kg in group A1; . Sm-h dose was 5g crude drug /kg and propranolol dose was 10mg/kg. The experimental results showed that all animals in the control group developed VF after ISO injection, of which 96% died and 4% returned to normal. Intraperitoneal injection of 5g crude drug /kg of Salvia miltiorrhiza water extract (sm-h) into anesthetized or non anesthetized animals for 30 minutes can significantly reduce the displacement of J-point, prevent or reduce the occurrence of VF and the number of deaths caused by VF, and significantly improve the survival rate of rats (p< 0.05). In rats with VF, sm-h (5g crude drug /kg) was immediately injected intravenously, 71% of which could temporarily restore sinus rhythm, indicating that sm-h has a certain preventive and therapeutic effect on VF, and can significantly prolong the survival time of VF animals. （P<0.05）。

2.2.8. effect of Salvia miltiorrhiza injection on the survival period of heart allograft in experimental animals: 2.2.8.1. effect of Salvia miltiorrhiza on the survival period of heart allograft in rats: male SD rats, weighing 300-400g as the recipient, Wistan as the donor, regardless of female body, weighing 200-300g, were subjected to abdominal heart transplantation in rats. The operation was performed according to the method introduced by Ono and chenzhonghua. The vena cava of the donor heart was ligated with the pulmonary vein, while the aorta was end-to-side anastomosed with the abdominal main vein of the recipient, and the pulmonary artery was end-to-side anastomosed with the inferior vena cava of the recipient. The experiment was divided into three groups, blank control group; A total of 15 rats were not given drugs; Salvia miltiorrhiza group 1, a total of 11 rats, were given Salvia miltiorrhiza injection 12g/kg daily intramuscularly from the day of transplantation; . The results showed that both doses of Salvia miltiorrhiza injection could significantly prolong the survival of transplanted hearts in rats. There was no significant difference in the survival time of the transplanted heart between the two doses. .

2.2.8.2. effect of Salvia miltiorrhiza on the rejection of rabbit heart transplantation: the animals are hybrid rabbits, the recipient weight is 1.8-3.2kg, the donor weight is 0.4-0.9kg, the donor and recipient gender is the same, the rabbit neck heart transplantation, using the literature method, the vena cava of the donor heart and pulmonary vein ligation, while the aorta and the recipient carotid artery end-to-side anastomosis, pulmonary artery and the recipient external jugular vein end-to-side anastomosis. Palpation of the heart beat and electrocardiogram were recorded every day after the operation. The end point of graft rejection was the disappearance of electrocardiogram. The rabbits were divided into four groups for the experiment, namely blank control group, with a total of 18 rabbits, without drug administration; Salvia miltiorrhiza group; A total of 6 rats were injected with Danshen injection at a dose of 6b/kg per day intramuscularly. When palpation of the transplanted heart beat was significantly weakened, it was changed to intravenous injection at a dose of 12g/kg per day; In the western medicine group, a total of 10 rats were injected with prednisolone 5mg/kg intramuscularly on the day, 2, 4, 6, 8, 11, 14, 17 and 20 after operation; Salvia miltiorrhiza combined with western medicine group; A total of 8 rats were given Danshen injection according to the Danshen group, and prednisolone according to the western medicine group.

The experimental results showed that Salvia miltiorrhiza injection could prolong the survival time of rabbit heart transplantation, but the statistical significance was not significant. However, when combined with prednisolone, the feint time of heart transplantation was significantly longer than that when the two drugs were used alone (p< 0.05), suggesting that Salvia miltiorrhiza injection can indeed enhance the anti graft rejection effect of corticosteroids.

3. effect on microcirculation disorder: 3.1. effect of Salvia miltiorrhiza injection on mesenteric microcirculation in dogs: under sodium thiophenate anesthesia, 6-8kg dogs were used in the experiment. Blood pressure and ECG changes were monitored by electrocardiograph and arterial cannula. At the same time, the abdominal cavity was opened to expose the mesentery, and the mesentery was fixed under the differential laser Doppler scattering system and laser Doppler microscope optical system. Find a blood vessel with a diameter of about 14-20u, use 10% glucose solution to keep the vein unobstructed at a rate of L5 drops per minute, and then quickly inject 0.5ml Danshen injection per kilogram of body weight through a percutaneous tube. Observe the blood flow velocity, blood pressure and ECG changes every 5 minutes. After the blood flow velocity returned to the original level for 2 hours, 0.5ml Yinhuang Injection per kilogram of body weight was injected to observe the blood flow velocity. Blood pressure and ECG changes. The effect of Danshen Injection on microcirculation was observed in 11 dogs after injection of Yinhuang Injection for 2 hours. During the whole experiment, the same microcirculatory blood vessels were fixed and observed. The results showed that. ; 0.492 ± 0.025; 0.553 ± 0.025; 0.526 ± 0.04 and 0.508 ± 0.04mm/s, (5', 10'p< 0.001; 15'p< 0.005; 20'p< 0.05; in 11 dogs, there was no significant difference (p> 0.05). Salvia miltiorrhiza and Yinhuang Injection have short-term effects on accelerating microcirculation blood flow.

- Effects of dihydroxyphenyl) lactic acid on microvessels in rabbits with microcirculation disorders: the rabbit model of microcirculation disorders was reproduced by intravenous injection of 10% high molecular dextran, and the effects of Danshensu, a water-soluble component of Salvia miltiorrhiza, on its microvessels and plasma lactic acid content were observed. The results showed that intravenous injection of different doses of Danshen injection and danshensu injection (without tween) could increase the intersection count of ocular conjunctiva and mesenteric microvessels in rabbits with microcirculation disorders (while the normal saline control group had no effect). This change was conducive to increasing the blood perfusion of local tissue microcirculation and establishing collateral circulation. The cases of decrease in plasma lactic acid content in rabbits in Danshen injection and danshensu injection groups were more than those in saline control after 30 minutes of treatment.There was no significant difference between the groups after 2 hours of treatment. The change of plasma lactate content is related to the degree of microcirculation disorder, and it is also one of the indicators reflecting the disorder of cell metabolism. This result further shows that Salvia miltiorrhiza and danshensu can improve the microcirculation disorder, thereby improving the metabolic disorder caused by cellular ischemia and hypoxia.

3.3. effect of Salvia miltiorrhiza on buccal pouch microcirculation of golden hamsters: Seventeen Syrian golden hamsters of either sex weighing 90-130g were used in the experiment. The preparation method of hamster cheek pouch specimen is the same as before. . The caliber and flow velocity of the accompanying micro motion, vein (the caliber is selected to be about 30um and 40um respectively) and capillaries with active blood flow were measured, photographed and recorded, and the flow pattern and the number of capillaries appearing on the screen were observed and recorded. During the experiment, 50ul (5ug/100ul) of norepinephrine (NA) was instilled locally into the cheek pouch to constrict the blood vessels and slow down the blood flow. The above measurements were made before and 1, 3, 5, and 10 minutes after the Na instillation. After that, Salvia miltiorrhiza (containing crude drug 5g/ml) was dripped into the same part according to different groups, and the above determination was made at 1, 3, 5, 10, 20, and 30 minutes after dropping. . The flow rate, flow and capillaries of microcirculation were improved. Secondly, the situation of venules is similar. It is suggested that Salvia miltiorrhiza can not only relieve microvascular spasm, but also improve microcirculation through other factors. Whether its inhibition of microvascular contraction caused by Na has the effect of blocking receptors is worthy of further discussion.

Cheng Zhangbi et al reported that local infusion of norepinephrine (NA) caused mesenteric microcirculation disturbance in mice weighing about 24g. After application of Danshensu, it could expand the contracted mesenteric arterioles, accelerate blood flow velocity, and thus eliminate mesenteric blood stasis.

3.4. effect of Salvia miltiorrhiza on experimental hepatic microcirculation disorder: Kunming healthy male mice, weighing 20 ± 2G, were anesthetized intraperitoneally with 10% urethane and laparotomized. The active part of microcirculation was selected, and 10ug epinephrine was dropped on the surface to block hepatic microcirculation, and then Salvia miltiorrhiza injection was dropped. The results showed that it had a good correction effect on hepatic microcirculation disorder (p< o.01).

4. effects on platelet aggregation and coagulation function: 4.1. effects of sodium tanshinone Ⅱ a sulfonate on thrombosis, platelet and coagulation function: both male and female experimental animals were used. The weight of rats was 200 ± (SN) 25g, and the weight of mice was 24.0 ± 1.4g. Blood sample collection: rats or mice were anesthetized by intraperitoneal injection of urethane 1g/kg. Blood was taken from the plastic cannula of cervical a, about 2ml each time, and the control group was injected with normal saline. In vitro thrombus formation was determined according to the chardle method; Platelet agglutination function was measured by turbidimetry and slide method.

Determination of coagulation function: recalcification time (RT), prothrombin time (PT) and kaolin partial thromboplastin time (kptt) were improved as follows: 25ul of sodium citrate anticoagulant slurry was placed in a 37 ℃ glass plate, after adding the reagent, it was continuously picked up with a needle, the time when filaments appeared was recorded, and the average value was calculated for 2-3 times. The results showed that there was no significant change in thrombosis, platelet and coagulation function in the control group before and 60 minutes after treatment. In the intravenous injection of sodium tanshinone Ⅱ a sulfonate 38mg/kg group, the thrombosis time in vitro was prolonged, the thrombus length was shortened, and the thrombus weight (wet weight and dry weight) was reduced 60 minutes after injection; The function of platelet adhesion and aggregation decreased; RT, Pt and kptt were prolonged, and the difference was significant compared with that before administration. In the intravenous injection of 25mg/kg group, the thrombosis time was prolonged, the dry weight of thrombus was reduced, and the platelet adhesion and aggregation function were reduced, which were significantly different from that before administration. However, the coagulation functions such as RT, Pt and kptt only tended to be prolonged. 60 minutes after injection in the intravenous injection of 6.25mg/kg group, p< except the platelet adhesion and aggregation function were reduced; The results of the three batches of experiments were basically the same, but the effective amount of anticoagulation was 38mg/kg in the first experiment, 12.5mg/kg in the first experiment, and 5mg/kg in the second experiment. ; 0.05, except for p< 0.01). It is suggested that sodium tanshinone Ⅱ a sulfonate has inhibitory effects on thrombosis, platelet and coagulation function in vitro in rats and mice, and the antiplatelet effect is stronger than the anticoagulant effect.

4.2. effect of Danshensu on coagulation function: 15 normal rabbits, male. They were divided into experimental group (9 rats) and control group (6 rats). The experimental group was injected with Salvia miltiorrhiza injection (100mg Danshensu per 1ml) 20mg / kg via ear vein, and the control group was injected with 0.85% sodium chloride solution (ph4.8). Before injection and at 30 minutes, 60 minutes, 90 minutes and 4.5 hours after injection, 3.5ml of blood was taken from the heart, and the in vitro thrombosis, platelet count, platelet function, coagulation function and fibrinolytic activity were determined according to the literature method. . These effects peaked at 30 minutes after an intravenous injection of mg/kg in rabbits and maintained for about 1 hour; Gradual recovery. At 4.5 hours after injection, all patients recovered to normal except for the in vitro thrombosis test.

4.3. effect of Danshensu on the release of vascular substances from platelets: the biological identification method of isolated rabbit aortic strips was used to observe the changes in the ability of rat platelets to release aortic contractile substances 1 hour before and after intravenous injection of Danshensu (10mg/100g body weight). The results showed that Salvia miltiorrhiza could significantly inhibit the release of vasoconstrictors from platelets. When rats were injected with Danshensu 100mg/kg intravenously, the rat platelet rich plasma was taken and incubated with ADP in the stomach. This incubation solution can significantly reduce the contraction height of isolated rabbit aortic strips, and the contraction height is 0.1? Mol norepinephrine was 38 ± 22%, and the contraction time was also significantly shortened. ? Mol norepinephrine 107 ± 26%, the Krebs solution of nutrient aortic strips was added with receptor blockers, anticholinergic and antihistamines, without anti-txa2 and other prostaglandins, and the incubation solution of the control group was retested. The contraction height of the aorta was 21 ± 16mm. If the incubation solution after tanshinol was given, the contraction height was reduced to 0.9 ± 1.5mm. The results suggested that tanshinol could inhibit the synthesis of platelet TXA2 and the release of prostaglandin vasoconstrictors. It is also reported that Danshen injection can inhibit add induced platelet aggregation: reduce platelet viscosity, resist thrombosis and coagulation, and also promote fibrinolysis. It is believed that the active ingredients in Danshen injection do not interact with platelet a receptor, mainly through inhibiting the activity of cyclic nucleotide phosphodiesterase. Increases cyclic nucleotides in platelets, thereby inhibiting platelet aggregation and 5-MT release.

5. effect on red blood cell membrane: put rabbit red blood cells into 0.60%nacl solution, and the red blood cells begin to rupture and hemolysis occurs. When it is reduced to 0.4%, all red blood cells rupture, and hemolysis reaches the maximum value. The test takes the hemolysis of red blood cells in 0.45%nacl solution as 100%. Add 0.1mg/ml sodium tanshinone Ⅱ a sulfonate to the above hypotonic solution, and only 34% hemolysis occurs, which proves that the drug has a certain protective effect on red blood cell membrane. Sodium tanshinone Ⅱ a sulfonate not only has a protective effect on hypotonic red blood cell membrane hemolysis, but also has a protective effect on hemolysis caused by heat (50 ℃), low pH, and saponin, and immune lymphoid cells.Hemolysis of sheep red blood cells also plays a role. The results showed that sodium tanshinone Ⅱ a sulfonate had obvious protective effect on hemolysis caused by five methods, while propranolol only protected hypotonic hemolysis, and had no obvious antagonism to the other four hemolysis. . When sodium tanshinone Ⅱ a sulfonate was added to the hypotonic solution, almost half of the cells did not rupture. Keeping its biconcave shape, the number of round dentate erythrocytes increased significantly, and there were no pore like depressions or small undulating cells on the surface, suggesting that its protective effect was due to the reduction of swelling degree in erythrocytes, rather than no rupture after swelling, which might be caused by the increase of tangential tension of cells.

According to another report, adding sodium tanshinone Ⅱ a sulfonate to cardiopulmonary bypass can reduce the damage of blood cells. The experimental dogs were divided into control and administration groups. When partial cardiopulmonary bypass was established, blood was taken immediately after the end of bypass to make scanning electron microscopy specimens. Results more than 90% of the red blood cells in the control group were in the shape of double concave disc with smooth surface before bypass, and a few were in the shape of round teeth, target, mouth and irregular shape. After partial cardiopulmonary bypass, the smoothness of the red blood cell surface was significantly changed. Abnormal red blood cells increased significantly. Up to 20%, especially the increase of round tooth shape and target shape. Most red blood cells in the administration group still maintained normal morphology, and a few red blood cells became less smooth on the surface, but the degree was significantly lower than that in the control group. Due to the destruction of blood cell components during cardiopulmonary bypass, micro thrombus was caused. This is closely related to the blood supply and recovery of organs after surgery.

6. effect on respiratory system: 6.1. protective effect of Salvia miltiorrhiza on bleomycin induced pulmonary fibrosis: 45 Kunming mice were used in the experiment. They weighed 18-20g and were randomly divided into three groups. Normal control group: no treatment; Bleomycin alone: 0.05ml (0.1mg) of bleomycin was injected intratracheally, and 0.05ml of normal saline was injected intramuscularly every day for 1 month from the second day (the injection was stopped once on Sunday); Salvia miltiorrhiza treatment group: 0.5ml of Salvia miltiorrhiza injection was intramuscularly injected every day from the second day of intratracheal injection of bleomycin (the injection was stopped once on Sunday). One month after bleomycin injection, all three groups of animals were sacrificed. . . It can be seen that under the experimental conditions, the protective effect of Salvia miltiorrhiza injection on pulmonary fibrosis is ideal.

6.2. effect of Salvia miltiorrhiza injection on preventing radiation-induced lung injury: Kunming mice, weighing 18-24g, 44 in total, were grouped according to hunger. An animal model of radiation-induced lung injury was established by irradiating the right chest of mice with deep X-ray. In the treatment group, 0.2ml of Salvia miltiorrhiza injection (containing 0.16g crude drug) was intraperitoneally injected 20 days before irradiation, once every other day, for a total of 10 times. The animals in each group were sacrificed in batches on the 10th day after irradiation and 1, 3, and 6 months after irradiation. The right lung was taken for tissue sections, stained with he and vangieson, and observed under the microscope. The results showed that after X-ray irradiation, the lung injury of mice in the treatment group was mild and the damage repair was fast; There was no significant difference in the changes of thymus tissue between the two groups. . But it has no obvious protective effect on thymus. The mechanism may be related to the function of Salvia miltiorrhiza in improving the resistance of vascular endothelial cells to radiation, reducing capillary permeability and improving microcirculation.

6.3. protective effect of Salvia miltiorrhiza on early lung injury caused by massive acute hemorrhagic necrotizing pancreatitis: dogs weighing 7.5-11kg were used in the experiment. Annp (acute hemorrhagic necrotizing pancreatitis) model was made by retrograde pancreatic duct injection of 5% sodium taurocholate 1ml/kg, and then Salvia miltiorrhiza (5g/kg) and normal saline were given intravenously. .

6.4. preventive effect of Salvia miltiorrhiza on oleic acid-induced respiratory distress syndrome: 62 male Wistar rats. The weight of 194.68 ± 22.4g (SX ± SD) was randomly divided into group A and saline control group (n = 10); Group B: oleic acid experimental group (N-13); Group C dexamethasone prophylaxis group (n = 13); Group D, Salvia miltiorrhiza prevention group (n = 13); In group A, 0.1ml/kg normal saline was injected into the tail vein as a negative control. . In group C-D, dexamethasone 2mg/kg and Salvia miltiorrhiza injection 1.5g/kg were injected intraperitoneally 15 minutes before oleic acid injection. Group B received no treatment before oleic acid injection as a positive control. Six hours after oleic acid injection, all rats were quickly sacrificed by decapitation method, and the lung tissue was immediately removed to measure the wet weight of the lung. Calculate the lung coefficient and record the macroscopic changes. Take a piece of lung tissue from the upper and lower parts of the left and right lungs respectively. If there are special lesions and obvious lesions in other parts of the lung, take another material from the lesion. The specimens were fixed in 10% formalin, embedded in paraffin, sectioned, and stained with he for light microscopic observation. The results showed that although there were different degrees of hemorrhage, congestion, consolidation and infarction on the lung surface in oleic acid experimental group (group B) and each prevention group, the macroscopic lesions of lung tissue in each prevention group were significantly lighter than those in the experimental group. If the number of scattered punctate lesions, marginal lesions, and marginal lesions with large patches were expressed as light, medium, and heavy according to the degree of lesions, 9 / 13 (69%) of the oleic acid group showed severe changes, while only 1 case of severe changes occurred in the salvia miltiorrhiza group in each prevention group, accounting for 8% of the salvia miltiorrhiza group; None of the cases in oleic acid group showed mild changes, while the mild changes in prevention group C-D group were 5 / 13 (39%), 4 / 13 (31%) and 3 / 13 (23%), respectively. The rest showed mainly marginal lesions. The most obvious lesion is at the edge, which may be related to peripheral artery embolism and spasm. The lung coefficient results showed that the lung coefficient of oleic acid group was significantly greater than that of the prevention groups, and the difference was very significant after statistical treatment (p< 0.01), but there was no significant difference between the prevention groups (p< 0.05). . The preventive effect is similar to that of dexamethasone. It is believed that early preventive application of Salvia miltiorrhiza can reduce or prevent the occurrence of respiratory distress syndrome (RDS).

7. effect on blood lipids and atherosclerotic plaque formation: 7.1. inhibitory effect of Danshensu on endogenous cholesterol (CH) synthesis: amphotericin B can form a complex with ch on animal cell membrane, which can make micropores appear on the cell membrane, and then lead to cell death. , .

7.2. effect of Danshensu on the production of oxidized low-density lipoprotein (LDL): the oxidized LDL prepared by adding Danshensu is called Danshensu oldl according to Wieland's method; . Determined according to the method of Schuh et al, Ex515nm，Em553nm。 The results showed that the electrophoretic mobility of natural LDL (nldl) and tanshinol oldl were less than that of oldl and had significant difference (p< 0.05), while tanshinol oldl had no significant difference compared with nldl (p> 0.05). See table 18 for the content of lipid peroxide (expressed in MDA) in various LDLs. The MDA content in tanshinol oldl was significantly lower than that in LDL group. The MDA content in tanshinol oldl was slightly lower than that in ve-oldl group, but there was no significant difference between the two groups, suggesting that tanshinol can be used for the prevention and treatment of atherosclerosis.

8. antibacterial and anti-inflammatory effects: 8.1. antibacterial effect of total tanshinone: in vitro antibacterial test, it was found that total tanshinone, an ether extract of Salvia miltiorrhiza, had strong antibacterial effect on Staphylococcus aureus and its drug-resistant strains. The total tanshinone contained 10 monomers, and the bacteriostatic tests were carried out respectively. Cryptotanshinone, dihydrotanshinone Ⅰ, hydroxytanshinone Ⅱ - A, tanshinone Ⅱ B and methyl tanshinate had bacteriostatic effects. Tanshinone Ⅱ a, tanshinone Ⅰ, tanshinone a, B and C had no antibacterial effect. The total tanshinone was also sensitive to 8 strains of penicillin, streptomycin and aureomycin resistant Staphylococcus aureus and 50 strains of erythromycin resistant Staphylococcus aureus. The minimum inhibitory concentration of total tanshinone (62.5ug/ml) was stronger than the maximum concentration of berberine (500ug/ml). Total tanshinone and its monomers have different degrees of antibacterial effect on human tuberculosis H37Rv, especially the effect of tanshinone A is the strongest. The results of the study on the relationship between the chemical structure and the activity of inhibiting human tuberculosis showed that tanshinone Ⅰ, which belongs to phenanthraquinone, cryptotanshinone, which belongs to o-quinone, and tanshinone IIA, which is between the two, have strong activities. It is believed that the antibacterial effect of diterpenoid quinones requires a certain degree of fat solubility. If polar groups are introduced into the parent nucleus, the activity will decrease. . The subthreshold dose of chlortetracycline and 0.5ml of 2% total tanshinone suspension were combined. The results showed that tanshinone could enhance the protective effect of aureomycin on Staphylococcus aureus infected mice.

8.2. inhibitory effect of Tanshinone on arthrogryposis in rats: 8.2.1. effect on egg white arthrogryposis in rats: 20 male rats weighing 200-230g were randomly divided into two groups: the administration group was given 2% tanshinone suspension by gavage of 2.0ml; the control group was given the same amount of starch suspension. . Two prophylactic administrations were given 1 day after administration, with an interval of 7 hours. One hour after administration, 0.1ml fresh egg white was injected into the palm skin of the right hind foot of rats, and the circumference of the left ankle joint was measured immediately after injection. The perimeter of the swollen right ankle joint was measured at 1, 2, 3, 4, 5 and 6 hours after the injection of egg white. The difference between the left and right perimeter was the degree of swelling. The two groups were statistically compared at each time. The results showed that tanshinone could significantly inhibit the egg white induced arthritis in rats.

8.2.2. effects on carrageenan arthrogryposis in rats: 20 female rats weighing 170-220g were randomly divided into two groups. Before the experiment, the administration group was given 2% tanshinone suspension for two days, twice a day, with an interval of 7 hours, and each rat was gavaged with 2.0ml each time. The control group was given the same amount of starch suspension. 0.1ml of 1% carrageenan was subcutaneously injected into the right hind paw of rats 30 minutes after administration on the day of the experiment, and the volume of the left foot was measured by the drainage method immediately after the injection of the inflammatory agent. The volume of the right foot was measured once at 1, 2, 3, 4, 5 and 6 minutes after inflammation, and then administered once after the time measurement at the third hour. The administration group was statistically compared with the control group. The results showed that tanshinone had a significant inhibitory effect on carrageenan induced arthrogryposis in rats, and the results measured at each time were statistically significant.

8.2.3. effect on dextran arthrogryposis in rats: 20 female rats weighing 170-200g were randomly divided into two groups. . 0.1ml of 6% dextran was subcutaneously injected into the right hind paw of each rat to cause inflammation. The volume of the right hind paw of rats was re measured at 1, 3, 5 and 7 hours after inflammation. The swelling degree was calculated by subtracting the volume of the left foot from the volume of the right foot at each time. The swelling degree of the two groups was statistically significant within 1, 3, 5 and 7 hours, indicating that tanshinone has obvious inhibitory effect on dextran induced arthritis in rats.

8.2.4. effect on formaldehyde induced arthritis in rats: 20 female rats weighing 180-230g were divided into two groups. The method of administration is exactly the same as that of carrageenan arthritis experiment. . The results showed that there was no significant difference between the two groups at 1 hour, but there were significant differences between the two groups at 3, 5, 7, 24 and 48 hours. The control group started to recover spontaneously at 72 hours, and recovered more rapidly at 96 hours. These results indicate that tanshinone has obvious inhibitory effect on formaldehyde induced subacute arthrogryposis.

8.2.5. experimental therapeutic effect on infectious arthritis in rats: male rats, weighing 120-160g, 10 rats in each group. The bacterial solution and drug are the same as the experimental treatment of mice. Make a 1:1 dilution of the bacterial solution after 18 hours of culture for standby. .

. The treatment group was intramuscularly injected with 1ml of Salvia miltiorrhiza injection, and then subcutaneously injected with 0.1ml of 1% carrageenan into the plantar region 30 minutes later, while the control group was intramuscularly injected with the same amount of normal saline. The results showed that Danshen injection could significantly reduce edema, and the swelling inhibition rate was 51%.

8.4. effect on formaldehyde peritonitis in rats: 20 male rats weighing 170-200g were divided into two groups. Each rat was intraperitoneally injected with 1.0ml of 2% formaldehyde solution, and sacrificed 36 hours later. The peritoneal exudate was extracted and the volume was recorded. The two groups were statistically analyzed. Tanshinone group was given once 30 minutes before formaldehyde injection. . The results showed that tanshinone had obvious anti exudative effect on formaldehyde induced peritonitis in rats. The anti-inflammatory mechanism of Salvia miltiorrhiza is not clear. It has been reported that Salvia miltiorrhiza injection significantly reduces neutrophil chemotaxis in rats and inhibits the release of lysosomal enzymes, which may be one of the anti-inflammatory links of Salvia miltiorrhiza. It was also reported that incubation of human leukocytes with total tanshinone for 1 hour could significantly inhibit leukocyte chemotaxis (directional movement of leukocytes in the direction of chemokines), but had no effect on the random movement of leukocytes (directional movement of leukocytes not affected by chemokines). If the incubation time was extended to 19 hours, 5ug/ml of total tanshinone was sufficient to significantly inhibit leukocyte chemotaxis and random movement, with inhibition rates of 79 and 81%, respectively. This result is consistent with tanshinone significantly inhibiting the migration of leukocytes to the inflammatory zone in vivo. .

9. protective effect on hepatocyte injury: 9.1. effect of Salvia miltiorrhiza on experimental liver regeneration: the experimental animal is white rat, weighing 180-220g, both male and female. Animals were divided into two groups. At 9-11 hours in the morning of the first day of the experiment, all animals except the normal group underwent partial hepatectomy under ether anesthesia. The left lobe and middle lobe of the liver (about 68% of the liver weight) were excised and weighed. In the afternoon of the day after operation and in the morning of the next day, the drug group was administered with 1ml/ mouse subcutaneously. At the 44th hour of the experiment, 1ml colchicine (containing 0.2mg) was injected intraperitoneally for 48 hours, and all animals were sacrificed. . Weigh the liver and calculate the regeneration degree. Small pieces of liver tissue were fixed in 10% formalin solution, embedded in paraffin, stained with hematoxylin eosin, and examined microscopically for histological observation, and the mitotic index was calculated. The experimental results showed that Salvia miltiorrhiza can increase the degree of liver regeneration, mitotic phase index and AFP detection rate, indicating that Salvia miltiorrhiza can promote liver regeneration. . On the basis of improving blood circulation in the whole body and local tissues, increasing portal blood flow and improving liver blood supply and nutrition may be important factors to promote liver regeneration. Liver regeneration is regulated by a variety of hormones, especially insulin and glucagon, which can significantly promote liver regeneration. Salvia miltiorrhiza and other blood activating and stasis removing drugs improve blood circulation. At the same time, it can bring more insulin and glucagon, which may also play a role in promoting liver regeneration.

9.2. effect of Salvia miltiorrhiza on acute liver injury in rats: take white rats, weighing 200-260g, both male and female. Experiments were performed in groups. . On the 1st and 5th days of the experiment, except for the normal group, the other two groups were subcutaneously injected with carbon tetrachloride 0.5ml/100g body weight. From the 2nd day of the experiment, the animals in each treatment group were given the drug, and the liver injury group was given the same amount of normal saline. On the seventh day of the experiment, all animals were fasted at 6 hours in the afternoon, and were gavaged with 50% glucose at 6 hours in the next morning, 2ml for each animal. After 2 hours, the animals were sacrificed, and part of the liver was quickly cut for glycogen and triglyceride determination; The remaining liver parts were fixed with 10% formalin solution, hematoxylin eosin staining (he) and fixed with Carnoy solution, and glycogen was revealed by PAS method. The serum was taken for determination of glutamic pyruvic transaminase (SGPT) and B lipoprotein. The SGPT activity of Salvia miltiorrhiza group was significantly lower than that of liver injury group (p< 0.01); ; The results of the determination of serum b-lipoprotein showed that there was no significant difference between the drug groups and the liver injury group. The glycogen content of liver homogenate in the administration group was similar to that in the liver injury group (p> 0.05). The liver glycogen content revealed by histochemical staining was generally consistent with the above determination results. The histopathological observation also showed that Salvia miltiorrhiza could significantly reduce liver necrosis and inflammatory reaction (p< 0.05 and p< 0.01).

9.3. preventive and therapeutic effects of Salvia miltiorrhiza on experimental liver cirrhosis: Rats weighing 200-320g, both male and female, were divided into groups according to the above experiments. Except for the normal group, all groups were fed with corn flour, mixed with 0.5% cholesterol (20% lard in the first 2 weeks), and 30% ethanol as a drink. On the first day of the experiment, except for the normal group, each animal in the other groups was subcutaneously injected with carbon tetrachloride 0.5ml/100g body weight, and then subcutaneously injected with carbon tetrachloride (40% vegetable oil solution) 0.3ml/100g body weight every three days. From the fifth week of the experiment, the administration group was given traditional Chinese medicine, and the control group was given the same amount of normal saline, and the animals were sacrificed at the end of the ninth week. The serum was taken for protein electrophoresis analysis, SGPT and fetal alpha globulin (AFP) detection (reverse hemagglutination method). The left lobe of liver was fixed in 10% formalin solution for hematoxylin eosin staining (he) and collagen fiber staining (VG); The rest of the liver was reserved for hydroxyproline determination for collagen content. The experimental results showed that Salvia miltiorrhiza administration group could significantly reduce the collagen content (p< 0.01) and serum r-globulin content. Hydroxyproline is the product of collagen degradation and is excreted in urine. Therefore, measuring the amount of urinary hydroxyproline can reflect the speed of collagen degradation in the liver.

. Collagen decomposition in vivo is mainly through the action of collagenase. In a neutral environment, collagenase can cleave collagen into two parts, one part of which is 3/4 large and one part of which is 1/4 small. The cleaved fragments are gradually decomposed by non-specific protease action. Therefore, the key of collagen degradation is closely related to the role of collagenase. Salvia miltiorrhiza can promote collagen degradation by increasing collagenase production or enhancing collagenase activity.

9.4. effect of Salvia miltiorrhiza on liver fiber reabsorption: Twenty three white rats weighing 170-210g, male and female, were divided into liver cirrhosis control group. Administration group and normal control group. On the first day of the experiment, the animals in the first two groups were subcutaneously injected with carbon tetrachloride 40.5ml/100g body weight, and then subcutaneously injected with the oil of carbon tetrachloride (40% vegetable oil solution) 0.3ml/100g body weight every three days. Simple corn flour (20% lard in the first 2 weeks) was fed with 0.5g% cholesterol, and 30% alcohol was the only drink. . At the end of 1, 2, and 3 weeks after administration, the 16 hour urine of animals in each group was collected to determine the content of urinary hydroxyproline. All animals were decapitated at the end of the llth week of the experiment. The sections were observed by jem100cx electron microscope. . The experimental results showed that the liver fibrosis of the animals treated with Salvia miltiorrhiza was significantly reduced compared with the control group, and the content of liver collagen was also significantly lower than that of the control group. It indicates that the drug can promote the reabsorption of liver fibers. As for the mechanism of Salvia miltiorrhiza alleviating liver fibrosis, it is still unclear. According to the existing data, Salvia miltiorrhiza inhibiting fibroproliferation is related to Salvia miltiorrhiza promoting the repair and timely regeneration of necrotic hepatocytes.

9.5. effect of Salvia miltiorrhiza injection on liver regeneration after partial hepatectomy in rats: female Wistar rats weighing 140-190g were fed a general diet and could not help drinking water before and after surgery. Weight was weighed before operation. The left and middle lobe of the liver were resected under mild ether anesthesia, and the resected liver was weighed. All operations were performed between 8:30-11:30 a.m. . From the day after the presentation, 0.66ml/animal of Salvia miltiorrhiza injection was intraperitoneally injected into the animals of each medication group at 4:00 p.m. every day. The animals in each group were sacrificed under ether anesthesia at 24 hours, 48 hours and 72 hours after surgery. All residual livers were removed, and the effects of Salvia miltiorrhiza injection on liver DNA synthesis rate, DNA content, hepatocyte marker nucleus number, hepatocyte division phase and regenerating liver weight after partial hepatectomy in rats were observed. The experimental results showed that Salvia miltiorrhiza injection can promote the DNA synthesis and cell division and proliferation process during liver regeneration, and has a certain role in promoting liver regeneration. This effect of Salvia miltiorrhiza may be achieved by improving the local blood circulation of the liver and strengthening the role of the intrinsic factors of liver regeneration.

Qixinguang et al observed the protective effect of Salvia miltiorrhiza on hepatocytes in rats with experimental liver injury. Through the pathological changes of liver in rats with liver injury under light and electron microscopy and the growth and decline of plasma fibronectin levels, it was shown that Salvia miltiorrhiza can stimulate the increase of plasma fibronectin (PFN) levels in rats, thereby improving the phagocytic function and opsonin activity of its reticular inner layer system, preventing liver immune injury, and achieving the effect of protecting hepatocytes and promoting hepatocyte regeneration. In recent years, many scholars have confirmed that plasma PFN is the main opsonin of the monocyte macrophage system. One of its main functions is to act as a mediator of phagocytosis in the reticuloendothelial system, and has opsonization effect on endotoxin and many liver damaging factors. It is suggested that Salvia miltiorrhiza can not only improve liver microcirculation and supply beneficial factors to the liver, but also improve PFN level, enhance phagocytic function and opsonin activity of reticuloendothelial system, avoid liver immune injury, and finally protect hepatocytes and promote the regeneration of hepatocytes.

10. effect of promoting tissue repair and regeneration: 10.1. effect of Salvia miltiorrhiza injection on calcium deposition in fracture healing in mice: adult male healthy mice were used in the experiment. The body weight was 25-35g, and the rate of bone formation was observed with 45Ca deposition as an indicator. A self-made fracture device was used to cause a closed fracture of the middle segment of the right femur in mice. After the fracture, 0.5ml of Salvia miltiorrhiza injection (oral) was given every day. Mice were sacrificed at 5, 7, 9 and 13 after administration. Forty eight hours before sacrifice, 0.2ml45ca calcium chloride solution was injected into the tail vein, and the radiation activities of the left and right femurs and the upper, middle and lower segments of the right tibia were measured. The results showed that the calcium deposition in the corresponding parts of the left and right bones was similar in normal mice; After the fracture of the middle segment of the right femur, the calcium deposition in the middle segment of the femur in the normal saline group and the salvia miltiorrhiza group increased continuously, while the upper and lower segments of the femur decreased instead, and the decrease was more significant in the salvia miltiorrhiza group. It shows that Salvia miltiorrhiza can mobilize more calcium than normal saline from adjacent bone tissue to better meet the needs of calcium for new bone formation, thus accelerating fracture healing.

Liujilan et al used C57BL purebred adult healthy mice to observe the effect of Salvia miltiorrhiza injection on calcium reabsorption in fracture healing in mice. The results showed that the radioactivity of the left and right femurs and the upper tibia of normal mice decreased with time; After the fracture of the middle segment of the right femur was caused by 45Ca injection at different times, the radioactivity of the fracture site in the normal saline group was lower than that of the corresponding healthy side; This change became more significant in the salvia miltiorrhiza group mice. Through electron microscope observation, it was found that the use of Salvia miltiorrhiza injection could make the formation of callus at the fracture site of rabbits earlier and more dense. ; In addition to the appearance changes, the protein synthesis activities of fibroblasts are more vigorous, the normal degeneration process of cells is also accelerated, and the extracellular collagen fibers are increased and enter the cytoplasm of fibroblasts; . Salvia miltiorrhiza can also promote fracture healing in the experiment of rabbit forelimb radius fracture.

10.2. effect of Salvia miltiorrhiza injection on the culture and growth of chicken embryo frontal bone isolated cells: for the preparation of chicken embryo frontal bone isolated cells, Leghorn chicken embryo frontal bone incubated for 12 days (remove the bone adventitia), cut and clean, and filter after trypsin digestion. The filtrate is the chicken embryo frontal bone isolated cell suspension. A total of about 3x103 cells were obtained by cell counting. Dilute the eagle medium (1) to 10ml, and then put it into five culture bottles (two slides in advance in each bottle), 2ml each. Then add 2ml each of eagle, 0.8% Salvia miltiorrhiza eagle, 0.4% Salvia miltiorrhiza eagle, 0.2% Salvia miltiorrhiza eagle and 0.1% Salvia miltiorrhiza Eagle culture solution.....The results showed that the method was simple and effective.The method was simple, and the method was simple, and the method was simple, and the method was simple..the method was simple, and the method was simple.The method was simple, and the method was simple.The method was simple, and the method was. They were divided into control group and 0.8, 0.4, 0.2 and 0.1 Salvia miltiorrhiza groups, and cultured in a 38 ℃ carbon dioxide incubator. The corresponding culture medium was changed three times a week and observed by inverted microscope day by day. The specimens were harvested on the 26th day of culture, stained and compared with the alkaline phosphatase acid phosphatase reaction (ALP ACP reaction for short). The experimental results showed that Salvia miltiorrhiza could promote the maturation of osteocyte like cells, secrete collagenous substances and AIP, and make calcium salt deposit on the collagen matrix to form bone nodules. However, too high concentration can lead to the inhibition of osteoblast like cell growth.

10.3. effect of Salvia miltiorrhiza on skin incision healing in rabbits: male rabbits weighing 2-3kg were used in the experiment and divided into control group; And Salvia miltiorrhiza group. All rabbits' right upper limbs were shaved with electric scissors. Under sodium pentobarbital intravenous anesthesia (30mg/kg) and aseptic technique, a full-thickness longitudinal incision was made in the middle and lower 1/3 part of the right anterior wall, about 1.5cm long, and the skin incision was sutured intermittently. The control group received 2ml of normal saline intramuscularly every day from the day of operation. The salvia miltiorrhiza group received 2ml of Salvia miltiorrhiza injection of the same batch number every day. The maximum number of injections was no more than 13. The injection was stopped on the day of slaughter. In the control group, two rabbits were taken from 1-10 days and 17, 21, 25 and 30 days after operation for serial observation; Two rabbits in the treatment group were taken on the 1st, 3rd, 5th, 7th, 9th, 13th, 17th, 21st, 25th and 30th day after the treatment for histological and histochemical comparative observation. The results showed that the appearance of macrophages and piles of foreign body giant cells in the salvia miltiorrhiza group was earlier than that in the control group, which significantly advanced the cleaning stage of wound repair, and continued to appear rich and congested capillaries. In addition, the appearance of vascular granulation tissue, collagen granulation tissue and scar granulation tissue in the salvia miltiorrhiza group was significantly earlier than that in the control group, indicating that the application of Salvia miltiorrhiza produced the effect of promoting blood circulation and removing blood stasis, and promoted the healing of skin incision.

. It may also affect the responsiveness of the body through the intrinsic regulatory mechanism.

11. anti tumor effect: 11.1. effect of Salvia miltiorrhiza on hematogenous dissemination of walker256 cancer cells in rats: young healthy rats weighing 65-85g, male. 2ml of each Salvia miltiorrhiza injection contains 3G of crude drug. With Walker 256 cancer cell ascites type, under sterile conditions, a small amount of cancerous ascites was drawn, counted by a hemocytometer, and diluted with normal saline to a concentration of 1-3x105/0.2ml. L-3x105 walker256 cancer cells were injected into the tail vein of rats. One hour before or 24 hours after cancer cell inoculation. . The animals were sacrificed 14-20 days after the inoculation of cancer cells. The body weight and lung weight were weighed, and the number of metastatic lesions on the lung surface was counted under a dissecting microscope. Red blood cell count and hematocrit were also measured in individual mice. . The experiment also observed that Salvia miltiorrhiza injection, whether 1ml, 1.5ml or 2.0ml, once a day for 4-5 days, and whether administered 1 hour before inoculation or (and) 24 hours after inoculation, could promote the metastasis of walker256 cancer cells from the blood circulation to the lung and other tissues. In addition to the lung, 1-2 tumor metastatic nodules were also observed on the surface of other organs during autopsy. The above experimental results suggest that Salvia miltiorrhiza injection can promote the hematogenous dissemination of Walker 256 cancer cells in rats. Due to the complex mechanism of cancer metastasis, it has not yet been fully elucidated. The effect of Salvia miltiorrhiza injection on hematogenous dissemination of walker256 cancer cells in rats is not necessarily suitable for human conditions. Therefore, the effect of Salvia miltiorrhiza injection on human tumor and other experimental animal tumor metastasis and its mechanism deserve further study.

. However, when the two drugs were combined, the inhibitory effect on tumor was strengthened. The tumor inhibition rate of cyclophosphamide alone group was 15.7% - 29.4%. Except for a group of animals with tumor inhibition rate of 17.9%, the tumor weight of the other two batches of experiments was not significantly different from that of the control group after statistical treatment (p< 0.05). The tumor inhibition rate of Salvia miltiorrhiza combined with cyclophosphamide group was 32.6-46.7%, which was significantly different from that of cyclophosphamide alone group, P value < 0.05 in two batches of experiments and p> in the other batch of experiments; 0.1. In order to explore the synergetic mechanism of Dan in the combination of cyclophosphamide, the nucleic acid content in tumor tissue was determined. The changes of nucleic acid content in tumor tissue were observed when the drugs were combined with each other, and there was no difference between the drugs alone. Results Salvia miltiorrhiza injection 4.5g/kg-9.0g/kg generally had no obvious effect on the DNA content in S-180 tumor tissue. When combined with low-dose cyclophosphamide, synergistic effect was seen in some experiments, so that the DNA content in tumor tissue was significantly reduced. But in other experiments, the DNA reduction was not significant. Salvia miltiorrhiza alone or combined with cyclophosphamide had no effect on the RNA content of tumor tissue.

11.3. therapeutic effect of Salvia miltiorrhiza combined with cyclophosphamide on 615 mouse leukemia and Ehrlich ascites cancer mice: Salvia miltiorrhiza injection combined with cyclophosphamide was used to treat 615 mouse leukemia, and no synergistic effect of the combined medication was seen at the dose used. The treatment of Ehrlich ascites cancer showed adverse effects. At the doses of 4.5g/kg and 9.0g/kg, the survival time of animals was significantly shortened, and the amount of ascites was increased compared with the control group.

11.4. effect of Salvia miltiorrhiza on spontaneous lung metastasis of Lewis lung cancer in C57BL mice: C57BL mice were intramuscularly inoculated with Lewis lung cancer cells, and then intraperitoneally injected with Salvia miltiorrhiza (9.0g/kg) for 12-15 times. They were sacrificed at the third week, and the number of lung metastases and the weight of primary tumor were calculated. The results showed that Salvia miltiorrhiza could significantly promote the spontaneous metastasis of Lewis lung cancer cells, but had no effect on the growth of primary tumor. In addition, the content of sialic acid in serum of C57BL mice inoculated with Lewis lung cancer was significantly higher than that of normal mice. . Serum sialic acid increased slightly in the early stage, but then decreased to normal level. It showed that Salvia miltiorrhiza had an inhibitory effect on the increase of serum sialic acid. Salvia miltiorrhiza at 9.0g/kg inhibited the sialic acid content of Lewis lung cancer cells (p< 0.05-0.02), but the inhibitory effect was not obvious at 4.5g/kg.

11.5. effect of Salvia miltiorrhiza injection on the surface of Ehrlich ascites cancer cells: six male mice weighing 20-30g were divided into two groups, three in the experimental group and three in the control group. All animals were intraperitoneally inoculated with Ehrlich ascites cancer cells. The experimental group was intraperitoneally injected with Salvia miltiorrhiza injection 50mg/10g body weight on the 4th day after inoculation, and the drug was administered for 4 consecutive days. The control group was intraperitoneally injected with sterilized normal saline during the same period. Ascites was collected from animals on the 8th day after inoculation of cancer cells. The electron microscopic observation of the prepared specimens showed that Salvia miltiorrhiza had a strong effect on the surface of cancer cells, and it could prevent the interaction between plant lectins and receptors on the surface of cancer cells. Using positively charged ferritin as a marker to study the change of cell surface charge, it was found that Salvia miltiorrhiza could not only increase the surface charge density of Ehrlich ascites cancer cells, but also change the charge distribution. Because the increase of cell surface charge density increases the repulsive force between cells and reduces the adhesion between cells, the result is that cells are easy to free and spread. This phenomenon explains one reason why Salvia miltiorrhiza promotes the spread of tumor cells. In addition, Salvia miltiorrhiza can also change the decrease of the proportion of microvilli surface area of cancer cells in the whole plasma membrane surface, as well as the increase of microvilli polarization phenomenon, suggesting that Salvia miltiorrhiza can activate tumor cells to increase motility, and also affect the spread and metastasis of tumor cells. The mechanism of anti-tumor and promoting tumor metastasis of Salvia miltiorrhiza is not very clear. Some people believe that the anti-tumor mechanism of Salvia miltiorrhiza may be related to the adjustment of the functional disorder of the coagulation fibrinolysis platelet system of the tumor host and the positive impact on the host immune system, and it has cytotoxic effect on tumor cells through the impact on nucleic acid metabolism, but further research is needed to confirm.

12. effect on cyclic adenylate phosphodiesterase: in order to understand the individual differences in the activity of the target enzyme in rabbit tissues, the activity of CAPD in each organ was measured in 10 healthy rabbits. The rabbit was decapitated after being struck and fainted. The brain, heart and kidney were immediately removed and placed in crushed ice. Under 4 ℃, homogenates and supernatants were prepared according to organs. ; Kidney: 0.294 ± 0.043; Heart: 0.033 ± 0.011. (the vitality unit refers to the umol number of camp decomposed in 10mg fresh tissue within 10 minutes under the determination conditions.).

When observing the inhibitory effect of water extract of Salvia miltiorrhiza on animal tissues, in order to avoid individual differences, three rabbits and other animals were used as the enzyme source according to the homogenate supernatant (35000g) prepared in batches from the organs. The determination of CAPD in each tissue was divided into two groups: Salvia miltiorrhiza group, 10ul of Salvia miltiorrhiza water extract (equivalent to 0.5g of crude drug per 1ml) was added to each assay (containing 133ug of organic matter); The control group (i.e. the normal group), without Salvia miltiorrhiza extract. Each set of assays was repeated twice. . The activity of CAPD decreased by 15-68% when 10ul of Salvia miltiorrhiza aqueous solution was added to the enzyme reaction system. This inhibitory effect varies greatly between tissues of experimental animals. Among them, CAPD in uterus and bladder, brain and lung, which are mainly smooth muscle, are the most sensitive to the extract of Salvia miltiorrhiza, and the inhibition ratio is large. CAPD in liver and kidney are the worst to Salvia miltiorrhiza, while the spleen, heart and other tissues are between the two. According to the study of enzyme action kinetics, the water-soluble components of Salvia miltiorrhiza showed typical noncompetitive inhibition on rabbit brain CAPD and irreversible inhibition. 16 spots of the water-soluble extract of Salvia miltiorrhiza could be detected by silica gel G thin-layer chromatography, and the preliminary separation was carried out with organic solvents. The dose-response curves of rabbit brain CAPD purified from each separated part were determined, and the 50% inhibition dose was calculated. Results (1) among the water-soluble components of Salvia miltiorrhiza, the inhibition ability of each point with smaller polarity, such as part 3 (mainly spots 1-6, but also 8-12), was poor, 7.4 times worse than that of the water extract; (2) The inhibition of Part 4 was the strongest (mainly spot 13), and its 50% inhibition was 8ug/ml, 32 times stronger than theophylline. Fat soluble sodium tanshinone Ⅱ a sulfonate had no inhibitory effect on rabbit brain CAPD.

The above results show that the water-soluble components of Salvia miltiorrhiza can inhibit CAPD in vitro, and have specificity for different tissues. So the mechanism of action of Salvia miltiorrhiza may partly change the activity of CAPD in vivo, thereby changing cAMP levels to regulate metabolic processes.

13. effects on the central nervous system: 13.1. effects of Salvia miltiorrhiza water extract on the autonomous activities of mice: the animals were Swiss white mice, male, weighing 17-26g. They were only given chloral hydrate. The night before the experiment, the food and water supply were stopped, and the other animals were not fasted. . The salvia miltiorrhiza preparation used is the supernatant after water extraction and ethanol precipitation. When using, dilute it with normal saline to the required concentration and adjust it to pH7. The dosage of Salvia miltiorrhiza was calculated according to g/kg. Amphetamine, chlorpromazine, meperidone, pentobarbital, barbital and Salvia miltiorrhiza were administered intraperitoneally, and chloral hydrate was administered orally. The experiment showed that Salvia miltiorrhiza can significantly inhibit the spontaneous activity of mice, and the effect is proportional to the dose. The combination of mirtazone and chlorpromazine can enhance the inhibitory effect.

. 15-30 minutes after injection of Salvia miltiorrhiza, another 250mg/kg of chloral hydrate or 25mg/kg of pentobarbital sodium were given. Salvia miltiorrhiza was combined according to different doses. Results there were significant differences between the single administration group and the combined administration group. In order to further observe the synergistic effect of Salvia miltiorrhiza and sodium pentobarbital, one group of mice was given sodium pentobarbital alone, and the sd50 was calculated. The other group of mice was given Salvia miltiorrhiza 10g/kg first, and then injected sodium pentobarbital, and the movement of dose-response line was observed. Results Salvia miltiorrhiza reduced the sd50 of pentobarbital sodium from 38.5mg/kg to 21.6mg/kg. The effect of Salvia miltiorrhiza on enhancing pentobarbital sodium was dose related. Salvia miltiorrhiza 2.5g/kg and 5g/kg increased the sleep percentage of pentobarbital sodium 150mg/kg group from 20% to 40% and 90% respectively. The dose of sodium pentobarbital was reduced to 125mg/kg, and the enhancing effect of Salvia miltiorrhiza was also very obvious. Mice were given chloral hydrate 250mg/kg, and all animals were awake. If it is combined with Salvia miltiorrhiza, the central inhibitory effect of chloral hydrate is significantly enhanced, and this enhancing effect is proportional to the dose of Salvia miltiorrhiza.

13.3. anti convulsive effect of Salvia miltiorrhiza on strychnine: the experimental method is the same as above. 30-60 minutes after the injection of Salvia miltiorrhiza, mice were injected with caffeine, pentylenetetrazole, strychnine and - theophylline via tail vein, with a volume not exceeding 0.1ug/kg body weight. The half convulsive dose (CD50) was calculated by the upper and lower method. The results showed that the anti convulsive effect was not obvious, but it had obvious anti convulsive effect on the psychomotor excitatory effect of amphetamine. According to ancient documents, Salvia miltiorrhiza has the function of nourishing yin and calming mind, replenishing qi and relieving vexation, which is reasonable.

13.4. effect of Salvia miltiorrhiza on visceral discharges in the posterior thalamic nucleus of cats: 19 cats of either sex of 2.5-3kg were intubated for artificial respiration under light anesthesia with chloroaldose (60mg/kg). The model was made according to the method of literature 135. . The animals were sedated by injection of trisulfonate quaternary ammonium phenol (5mg/kg), and were given artificial respiration. The body temperature was maintained at 36-39 ℃ for experimental observation. First, the greater splanchnic nerve was stimulated with a strong single or double pulse to find the unit producing the evoked discharge of the greater splanchnic nerve in the P area. After finding the unit, Danshen injection was injected intravenously at different doses of 1.4-9g/kg, and the greater splanchnic nerve was stimulated every 3 minutes. The changes of P discharge before and after Danshen injection were observed. The results showed that Salvia miltiorrhiza could inhibit the visceral pain discharge of posterior thalamic nucleus, but directly acting on the nerve stem could not block its nerve excitation conduction, indicating that its analgesic effect was central.

It was also reported that 10-30 minutes after intravenous injection of 4.5g/kg Salvia miltiorrhiza in conscious rabbits, the spontaneous electrical activity of cerebral cortex was significantly reduced. . Repetitive stimulation of the rabbit cerebral cortex with strong electrical stimulation can cause rhythmic electrical activity. After the stimulation is stopped, the electrical activity can often last for several seconds to tens of minutes (i.e. post discharge). After intravenous injection of Salvia miltiorrhiza, the threshold of post discharge caused by electrical stimulation increased significantly, and recovered after about 50 minutes. In rabbits anesthetized with chloraldose and urea ester, the somatosensory motor area of one cerebral cortex was stimulated, and monopolar recordings were made at the symmetrical point of the contralateral cortex. An electrical response was generally positive first and then negative. Local administration of Salvia miltiorrhiza under the stimulating electrode or the recording electrode could increase the electrical response; When the drug is administered intravenously, the increase of electric reaction is more obvious. When a small dose of Salvia miltiorrhiza is injected intravenously, there is no obvious effect, but when a large dose of Salvia miltiorrhiza is injected, it produces a depressive effect. The above experimental results show that Salvia miltiorrhiza can reduce the amplitude of spontaneous electrical activity in the cerebral cortex, increase the firing threshold after repeated stimulation, reduce the repetitive electrical response in the cerebral cortex after single stimulation, reduce the amplitude of electrical activity in the cerebral cortex by H, and do not significantly increase the higher frequency components, so the reduction of electrical activity is not the result of desynchronization. Salvia miltiorrhiza can inhibit the activity of cyclic adenosine monophosphate diesterase in various tissues in vitro, especially the brain and lung. It is presumed that the inhibitory effect of cerebral cortex may be achieved by inhibiting the activity of cyclic adenosine monophosphate diesterase and increasing the level of cyclic adenosine monophosphate.

14. sex hormone like effect: 14.1. estrogen like activity of tanshinone: female young mice weighing 11-12g were randomly divided into four groups with 10 mice in each group. ; The control group was treated with 0.2ml of 3% starch paste by gavage once a day; The positive control group was subcutaneously injected with estradiol 0.25ug for 3 consecutive days. On the fourth day, the mice were sacrificed by cervical amputation and the uterus was removed. The adipose tissue was removed and the weight of uterus was weighed by tissue balance. Results the weight of uterus in the administration group was significantly higher than that in the control group. The effect of tanshinone given twice a day was more obvious than that given once, but its estrogen like activity was weaker than that of estradiol.

Another 60 adult female mice of 22-24g were selected and bilateral ovaries were excised. Three days later, the mice were divided into groups and treated with 2% tanshinone starch suspension by gavage twice a day, 0.5ml each time. The control group was given a considerable amount of 3% starch paste, and the positive control group was subcutaneously injected with estradiol, 0.25ug per mouse, for three consecutive days. On the fourth day, the mice were sacrificed by cutting their necks, and the uterus was weighed. Results the uterus weight of mice in tanshinone group was similar to that of the control group, while the uterus weight of mice given estradiol was significantly increased. It can be seen that the estrogen like activity of tanshinone is different from that of estradiol, and the former needs to function through the ovary. After tanshinone was given by gavage to adult female rats, the vaginal fragments showed estrous changes, which also proved that it had estrogen like activity.

14.2. antiandrogen activity of tanshinone: male rats weighing 50-60g were randomly divided into 4 groups on the fifth day after surgery, with 7 rats in each group. The tanshinone group was gavaged with 2% tanshinone starch suspension, twice a day, 10ml each time; the control group was given a comparable amount of 3% starch paste, and the dosage of the two drugs in the testosterone propionate plus tanshinone group was the same as the same. The animals were sacrificed on the sixth day, and the seminal vesicles and prostate were weighed, expressed as the weight of seminal vesicles and prostate /100g body weight. The results are shown in table 28. The weight of seminal vesicles and prostate in the testosterone propionate group was significantly higher than that in the other three groups, with statistical differences, indicating that tanshinone has the effect of anti testosterone propionate.

15. pharmacological effects of processed products: the traditional processing methods of Salvia miltiorrhiza include wine frying, vinegar frying and raw use. In order to explore the effects of different processing methods on drug efficacy, the experiment was conducted to observe the acute liver injury model of rabbits caused by carbon tetrachloride. Thirty healthy male rabbits weighing 2-2.5kg were randomly divided into control group, raw Salvia miltiorrhiza treatment group, wine fried Salvia miltiorrhiza treatment group and vinegar fried Salvia miltiorrhiza treatment group; The blood was collected from the rabbit heart, and the glutamic pyruvic transaminase (SGPT) was measured. Then carbon tetrachloride was subcutaneously injected once (0.5ml/kg). The next day, the treatment groups were gavaged with Danshen Decoction (5ml/kg), once a day, for 6 consecutive days. The control group was gavaged with cold tap water after boiling. The method was the same as that of the administration group. The next day after drug withdrawal, blood was taken again to measure SGPT, and the liver was immediately sacrificed, dissected and examined, and fixed with 10% formalin. . Some sections were stained with Sudan IV fat. Microscopic observation. At the end of the experiment, except for 3 animals that had accidents during the experiment, only 27 animals were left for analysis. Results after carbon tetrachloride injection, the liver appeared toxic hepatitis lesions of different degrees, the central venules of lobules were dilated and congested to different degrees, hepatocytes swelled and degenerated, punctate or focal necrosis, and inflammatory cell infiltration. Table 34 shows that compared with the control group, the medication group has the effect of reducing liver injury to different degrees. According to the rank sequence test, raw and wine fried Salvia miltiorrhiza can significantly reduce cell necrosis (p< 0.05 and p< 0.01). Microscopically, there was less necrosis of hepatocytes, mild cell degeneration, exposure of liver sinusoids, and less inflammatory cell infiltration. . . There was no significant difference between the two groups (p> 0.05). It is suggested that the effect of wine fried and vinegar fried Dan in raw products is not improved. This is suspicious for the clinical use of processed Salvia miltiorrhiza products in the future, which is worthy of further study.