阅读说明：本技术 一种治疗冠心病的药物组合物及其医药用途 (Pharmaceutical composition for treating coronary heart disease and medical application thereof ) 是由 杨洁 杨雪松 陈永志 曾庆娟 张倩 杨传华 于 2021-09-18 设计创作，主要内容包括：本发明属于中药技术领域,具体涉及一种用于治疗冠心病的中药组合物及其医药用途。所述中药组合物主要由细辛、香附、黄芪、党参、麦冬、五味子、郁金、水蛭、当归、川芎、海风藤、茯苓制备而成。本发明中药组合物、益气养阴、活血宣痹、行气止痛,可有效缓解胸痛、胸闷、气短、心悸、乏力等病症,具有较好的治疗冠心病心绞痛的功效,临床治疗冠心病的有效率可达80％,效果显著。(The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating coronary heart disease and medical application thereof. The traditional Chinese medicine composition is mainly prepared from asarum, rhizoma cyperi, astragalus mongholicus, codonopsis pilosula, radix ophiopogonis, schisandra chinensis, radix curcumae, leech, angelica sinensis, ligusticum wallichii, kadsura pepper stem and poria cocos. The traditional Chinese medicine composition has the effects of tonifying qi and nourishing yin, activating blood and freeing paralysis, and promoting qi circulation and relieving pain, can effectively relieve symptoms such as chest pain, chest distress, short breath, palpitation, hypodynamia and the like, has a good effect of treating coronary heart disease and angina pectoris, and has an effective rate of 80% in clinical treatment of coronary heart disease and an obvious effect.)

1. a Chinese medicinal composition for treating coronary heart disease is characterized by mainly comprising asarum, rhizoma cyperi, astragalus mongholicus, codonopsis pilosula, radix ophiopogonis, schisandra chinensis, radix curcumae, leech, angelica sinensis, ligusticum wallichii, kadsura pepper stem and poria cocos.

2. The traditional Chinese medicine composition of claim 1, which comprises the following components:

3. the traditional Chinese medicine composition of claim 2, wherein the traditional Chinese medicine composition comprises the following components:

4. the Chinese medicinal composition of any one of claims 1 to 3, wherein the Chinese medicinal composition can be prepared into a clinically acceptable preparation directly or after adding pharmaceutically acceptable auxiliary materials.

5. The traditional Chinese medicine composition of claim 4, wherein the clinically acceptable preparation is an oral solid preparation and/or a liquid preparation.

6. The Chinese medicinal composition of claim 5, wherein the solid preparation comprises but is not limited to granules, capsules, tablets; the liquid preparation includes but is not limited to oral liquid, mixture, syrup and decoction.

7. The use of the Chinese medicinal composition according to any one of claims 1 to 6 in the preparation of a medicament for the treatment of coronary heart disease.

8. A pharmaceutical composition for treating coronary heart disease, which comprises the Chinese medicinal composition of any one of claims 1 to 3.

9. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is a combination of the Chinese medicinal composition of any one of claims 1-3 and a chemical agent; preferably, the pharmaceutical composition is the combination of the traditional Chinese medicine composition of any one of claims 1 to 3 and a chemical drug for treating coronary heart disease.

10. The pharmaceutical composition of claim 8 or 9, wherein the pharmaceutical composition can be prepared into an oral preparation directly or after adding pharmaceutically acceptable auxiliary materials; preferably, the oral preparation includes but is not limited to granules, tablets, capsules, oral liquid and decoction.

Technical Field

The invention relates to a traditional Chinese medicine composition and medical application thereof, in particular to a pharmaceutical composition for treating coronary heart disease and application thereof in preparing a medicine for treating coronary heart disease, belonging to the field of medicines.

Background

Coronary atherosclerotic heart disease is a heart disease caused by myocardial ischemia, hypoxia or necrosis due to stenosis or obstruction of a blood vessel cavity caused by atherosclerotic lesions generated in coronary vessels, and is often referred to as "coronary heart disease". Coronary heart disease may be more widespread, but also includes inflammation, embolism and the like resulting in stenosis or occlusion of the lumen. The world health organization classifies coronary heart disease into 5 major categories: latent or asymptomatic coronary heart disease, angina pectoris, myocardial infarction, ischemic heart disease and sudden death in 5 clinical types. The clinical classification is often chronic myocardial ischemia syndrome and acute coronary syndrome.

Risk factors for coronary heart disease include modifiable risk factors and non-modifiable risk factors. Understanding and intervening risk factors can help prevent and treat coronary heart disease.

The risk factors that can be varied are: hypertension, dyslipidemia (total or low density lipoprotein cholesterol, triglycerides, high density lipoprotein cholesterol too low), overweight/obesity, hyperglycemia/diabetes, poor lifestyle including smoking, improper diet (high fat, high cholesterol, high calorie, etc.), lack of physical activity, excessive drinking, and psychosocial factors. The immutable risk factors are: gender, age, family history. Furthermore, infections such as cytomegalovirus, Chlamydia pneumoniae, helicobacter pylori, etc. are involved.

The onset of coronary heart disease is often associated with seasonal changes, emotional agitation, increased physical activity, satiety, heavy smoking and alcohol consumption, etc.

Disclosure of Invention

One of the purposes of the invention is to provide a traditional Chinese medicine composition and the application thereof in preparing a medicine for treating coronary heart disease;

the traditional Chinese medicine composition mainly comprises asarum, rhizoma cyperi, astragalus mongholicus, codonopsis pilosula, radix ophiopogonis, schisandra chinensis, radix curcumae, leech, angelica sinensis, ligusticum wallichii, kadsura pepper stem and poria cocos.

Specifically, the traditional Chinese medicine composition comprises the following components:

preferably, the traditional Chinese medicine composition contains the following components:

the traditional Chinese medicine composition can be prepared into a clinically acceptable preparation directly or after pharmaceutically acceptable auxiliary materials are added.

Preferably, the clinically acceptable preparation is an oral solid preparation and/or a liquid preparation.

Further preferably, the solid preparation includes but is not limited to granules, capsules, tablets; the liquid preparation includes but is not limited to oral liquid, mixture, syrup and decoction.

The second purpose of the invention is to provide the application of the traditional Chinese medicine composition in preparing a medicine for treating coronary heart disease.

The invention also aims to provide a pharmaceutical composition for treating coronary heart disease, which contains the traditional Chinese medicine composition.

The pharmaceutical composition for treating coronary heart disease provided by the invention can also contain chemical drugs for treating coronary heart disease.

The pharmaceutical composition for treating coronary heart disease provided by the invention can be a Chinese patent medicine preparation directly prepared from the Chinese medicinal composition or a Chinese and western medicine compound preparation prepared by adding chemical medicines for treating coronary heart disease in a clinical routine manner.

Specifically, the pharmaceutical composition for treating coronary heart disease can be prepared into an oral preparation directly or after pharmaceutically acceptable auxiliary materials are added; preferably, the oral preparation includes but is not limited to granules, tablets, capsules, oral liquid and decoction.

The traditional Chinese medicine composition disclosed by the invention is composed of asarum, rhizoma cyperi, astragalus, codonopsis pilosula, radix ophiopogonis, schisandra chinensis, radix curcumae, leech, angelica sinensis, ligusticum wallichii, kadsura pepper stem and poria cocos, can tonify qi and nourish yin, activate blood and disperse arthralgia, promote qi circulation and relieve pain, can effectively relieve symptoms such as chest pain, chest distress, short breath, palpitation and hypodynamia, and has a good effect of treating coronary heart disease and angina pectoris.

Clinical use effects prove that the traditional Chinese medicine composition has the advantages that the traditional Chinese medicine syndrome integral of chest pain, chest distress, palpitation, short breath and the like of a patient treated by the traditional Chinese medicine composition is obviously reduced, the attack frequency of angina pectoris is obviously reduced, the attack time is obviously shortened, the effective rate of clinical treatment can reach 80%, and the effect is obvious.

The pharmacological experiment results show that the traditional Chinese medicine composition has better treatment effect on experimental rat coronary heart disease, can promote myocardial blood supply, relieve blood hyperviscosity, relieve vascular sclerosis and the like; the preparation has the advantages of relieving the oxidative stress reaction of the rat subjected to myocardial ischemia reperfusion, enhancing the oxidation resistance of myocardial cells and having a better protection effect on the myocardial cells.

Drawings

FIG. 1: typical case 1 patient electrocardiogram before treatment: the V1-V3 ST segment is downwards moved by 0.05-0.1mV

FIG. 2: typical case 1 patient electrocardiogram after treatment: not seen ST changes

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The present invention is further illustrated by the following examples, which are intended to be purely exemplary and are not intended to limit the scope of the invention, as various equivalent modifications of the invention will occur to those skilled in the art upon reading the present disclosure and fall within the scope of the appended claims.

Example 1

Taking 1.8g of asarum, 7.8g of rhizoma cyperi, 16.5g of astragalus, 18.5g of codonopsis pilosula, 17.8g of radix ophiopogonis, 4.8g of schisandra chinensis, 7.5g of radix curcumae, 2.3g of leech, 8.3g of angelica, 7.7g of ligusticum wallichii, 7.6g of kadsura pepper stem and 12.5g of poria cocos, adding water for decoction, and filtering to obtain decoction which is taken twice a day in the morning and evening.

Example 2

Taking 18g of asarum, 78g of rhizoma cyperi, 165g of astragalus, 185g of codonopsis pilosula, 178g of radix ophiopogonis, 48g of schisandra chinensis, 75g of radix curcumae, 23g of leech, 83g of angelica sinensis, 77g of ligusticum wallichii, 76g of kadsura pepper stem and 125g of poria cocos, adding water for decoction, filtering decoction, concentrating the decoction into thick paste with the relative density of 1.35-1.40 (50 ℃), drying, crushing into fine powder, adding a proper amount of lactose powder and dextrin, uniformly mixing, granulating, drying, and preparing 1000g of granules.

Example 3

Taking 25g of asarum, 60g of rhizoma cyperi, 200g of astragalus, 150g of codonopsis pilosula, 300g of radix ophiopogonis, 30g of schisandra chinensis, 90g of radix curcumae, 15g of leech, 100g of angelica sinensis, 50g of ligusticum wallichii, 100g of kadsura pepper stem and 100g of poria cocos, adding water for decoction, filtering decoction, concentrating to obtain thick paste with the relative density of 1.35-1.40 (50 ℃), drying, crushing into fine powder, adding a proper amount of lactose powder and dextrin, uniformly mixing, granulating, drying, and preparing into 1000g of granules.

Example 4

Taking 12g of asarum, 100g of rhizoma cyperi, 120g of astragalus, 200g of codonopsis pilosula, 150g of radix ophiopogonis, 60g of schisandra chinensis, 50g of radix curcumae, 25g of leech, 50g of angelica sinensis, 90g of ligusticum wallichii, 60g of kadsura pepper stem and 150g of poria cocos, adding water for decoction, filtering decoction, concentrating until the relative density is 1.25-1.30 (55-60 ℃), drying, crushing into fine powder, adding a proper amount of starch, talcum powder and magnesium stearate, mixing uniformly, preparing into granules, drying, and pressing into 1000 tablets to obtain the tablet.

Example 5

Taking 20g of asarum, 70g of rhizoma cyperi, 180g of astragalus, 180g of codonopsis pilosula, 180g of radix ophiopogonis, 40g of schisandra chinensis, 80g of radix curcumae, 20g of leech, 90g of angelica sinensis, 70g of ligusticum wallichii, 80g of kadsura pepper stem and 120g of poria cocos, adding water for decoction, filtering decoction, concentrating the decoction into thick paste with the relative density not lower than 1.30(60 ℃), adding a proper amount of starch, uniformly mixing, drying, preparing into granules, filling into capsules, and preparing into 1000 capsules to obtain the capsules.

Example 6

Taking 15g of asarum, 85g of rhizoma cyperi, 150g of astragalus, 190g of codonopsis pilosula, 150g of radix ophiopogonis, 50g of schisandra chinensis, 70g of radix curcumae, 25g of leech, 70g of angelica, 80g of ligusticum wallichii, 70g of kadsura pepper stem and 130g of poria cocos, adding water for decoction, filtering decoction, adding a proper amount of sucrose and sodium benzoate, adding water to 1000ml, stirring uniformly, and subpackaging to obtain the oral liquid.

Second, clinical effect verification

The traditional Chinese medicine composition is derived from clinical experience prescriptions of hospitals, and has better clinical use effect.

1 data and method

1.1 general data

80 patients with coronary heart disease complicated with angina pectoris collected in 2019, 8-2021 and 3 are selected and randomly divided into a control group (40 cases) and an observation group (40 cases). The age of the patients in the control group is 53-68 years, and the average (61.4 +/-4.7) years; 21 men and 19 women; the disease course is 1.3-5.4 years, and the average (2.8 +/-1.4) years. The patients in the observation group are 55-70 years old, and the average (63.8 +/-5.2) years old; 20 male and 20 female; the disease course is 1.1-5.5 years, and the average (3.3 +/-2.1) years. The comparison of all basic data of 2 groups of patients has no statistical significance, and P is more than 0.05.

1.2 diagnostic criteria

Western medicine refers to the international health organization (WHO) and international society for cardiology (ISFC) revised CHD angina diagnostic criteria; the traditional Chinese medicine refers to the diagnosis standard of qi deficiency and blood stasis in the internal science of traditional Chinese medicine.

1.3 methods

1.3.1 methods of treatment

The control group is subjected to a conventional western medicine treatment scheme, aspirin is selected for oral administration, 100 mg/time and 1 time/d; isosorbide mononitrate tablets are orally taken at 20 mg/time and 2 times/d; atorvastatin is administered orally at a starting dose of 10mg 1 time a day, optionally adjusted according to the physician's prescription, at a dose interval of 4 weeks or more and a maximum dose of 80mg 1 time a day for 1 month of continuous treatment.

The observation group administered the decoction obtained in example 1 on the basis of the above treatment in two doses per day, 200 ml/dose, and administered in the morning and evening for 1 month continuously.

1.3.2 Observation index

Including the symptom integral of the traditional Chinese medicine, the attack time and frequency of angina pectoris, and comparing the comprehensive curative effects.

The Chinese medicine symptom integral is evaluated according to the relevant standards of the Chinese medicine new drug clinical research guiding principle, the symptom degree of a patient is mainly divided into 0, 1, 2 and 3 points, the total point is 18 points, and the higher the point is, the more serious the symptom is.

The time and frequency of angina pectoris attack before and after treatment were compared in two groups of patients.

The comprehensive curative effect can be divided into obvious effect (the symptom basically disappears, or the integral of the traditional Chinese medicine symptom is reduced by more than 60 percent, the electrocardiogram is basically normal), effective effect (the integral of the traditional Chinese medicine symptom is reduced by more than 40 percent, and the electrocardiogram shows improvement) and ineffective effect (the standard is not met). The total effective rate is significant efficiency + effective rate.

1.3.3 statistical methods

Processing data with SPSS22.0 software, checking the count data (%) by Chi-square, and measuring dataThen using t test, P < 0.05 indicates that the data difference is statistically significant.

2 results

2.1 Chinese medicine symptom integral comparison

Before treatment, the difference of the Chinese medicine symptom integrals of the 2 groups of cases has no obvious statistical significance (P is more than 0.05), but the Chinese medicine symptom integrals after the observation group is treated are obviously lower than those of the control group (P is less than 0.05). See table 1.

TABLE 12 comparison of the syndrome scores of TCM before and after treatment of the patients: (Minute)

2.2 comparison of angina pectoris attack time and frequency

Before treatment, the comparison difference of the angina pectoris attack time and the angina pectoris attack frequency of two groups of patients has no statistical significance (P is more than 0.05); after treatment, the attack time of angina pectoris in the observation group is shorter than that in the control group, the attack frequency is lower than that in the control group, and the difference has statistical significance (P is less than 0.05). See table 2.

TABLE 22 comparison of angina pectoris onset time and frequency before and after treatment

2.3 comparison of clinical comprehensive therapeutic effects

After treatment, the control group has 10 cases of obvious effect, 18 cases of effective effect and 12 cases of ineffective effect, and the total effective rate is 70 percent; the treatment group has 16 cases of obvious effect, 20 cases of effect and 4 cases of no effect, the total effective rate is 90 percent, and the total effective rate of patients in the treatment group is obviously higher than that in the control group. See table 3.

TABLE 32 group clinical efficacy comparisons

Group of	Number of examples	Obvious effect (example)	Effective (example)	Invalid (example)	Total effective rate (%)
						Control group	40	10	18	12	70.00
Observation group	40	16	20	4	90.00

Typical case 1: in a certain woman, 55 years old, Jinan people in Shandong province, patients have dizziness with chest pain, chest distress, short breath, palpitation and poor diet, and families bring the patients to Chinese medical hospital in Shandong province for examination, and electrocardiogram shows that: the V1-V3 ST segment is downwards moved by 0.05-0.1 mV; limb lead low voltage treatment method: after 2 courses of treatment of taking the medicine, the sensory symptoms of patients are relieved, after 2 courses of treatment, the self-sensory symptoms basically disappear, and after 1 month of treatment: limb lead low voltage; ST was not changed, and no recurrence occurred half a year later with follow-up.

Third, pharmacodynamics experiment

In order to verify the application and the mechanism of the traditional Chinese medicine composition in treating coronary heart disease, the inventor carries out related pharmacodynamic test research. It should be noted that the medicines selected in the pharmacodynamic tests below are the medicines obtained by the representative formula and the preparation method thereof; the inventor also conducts pharmacodynamic experiments on the medicines obtained by the other formulas and the preparation methods, and the experimental results show that the medicines obtained by the other formulas and the preparation methods have the same or similar effects, but the medicines are not exhaustive due to space limitations.

In addition, the pharmacodynamic experiments described below only take part of animal models as examples to verify the efficacy of the invention, and the inventor also performs related pharmacodynamic experiments on other types of coronary heart diseases mentioned in the invention, and the experimental results show that the coronary heart diseases have the same or similar effects, and are not exhaustive.

The inventor explains that the following experimental studies are carried out on the basis of the safety of the drug proved by acute toxicity tests and long-term toxicity tests, and the administration dose in the experimental studies is within a safe dose range.

First, the Chinese medicinal composition of the invention has the treatment effect on experimental rat coronary heart disease

1 Material

1.1 animals:

SD rat, SPF grade, 180-: SYXK (lu) 20180008, provided by lumnan pharmaceutical group ltd, was acclimatized for one week prior to the experiment.

1.2 drugs, reagents

1.2.1 medicaments

Formulations obtained in examples 2, 4 and 6 of the invention

Qi-tonifying dripping pill containing astragalus root and ginseng

1.2.3 dosage

Example 2 granules: 1.9g/kg (low dose), 2.7g/kg (medium dose), 5.4g/kg (high dose)

Example 4 tablets: 0.9g/kg

Example 6 oral liquid: 2.7ml/kg

Qishen Yiqi Wan (milkvetch root and Ginseng drop pill for benefiting Qi): 0.135g/kg

2. Modeling, grouping and administering drugs

80 rats are randomly divided into a blank group, a model group, a astragalus and ginseng qi-tonifying pill group, 3 dose groups in example 2 (high, medium and low), an example 4 group and an example 6 group. Except for the blank group, the abdominal cavities of the rats of other groups are injected with vitamin D3(60 ten thousand units/kg) at one time, and simultaneously, 10ml/kg of fat emulsion is infused every day for 10 weeks; at the same time of experiment, each administration group is administered with corresponding medicine by intragastric administration, and the blank group and the model group are administered with the same amount of normal saline by intragastric administration. 3 days before the experiment, except for a blank group, the rats of other groups are injected with 30U/kg of posterior pituitary in the abdominal cavity, 1 time per day for 3 consecutive days to induce coronary artery spasm, prepare a coronary heart disease model, and inject normal saline in the abdominal cavity of the blank group.

3 observation index

3.1 record the electrocardiogram 30min before model making and after the last administration.

3.2 recording ECG after last administration, rats were anesthetized, blood was taken from inferior vena cava, and serum or plasma was isolated.

3.2.1 inflammatory factor assay: measuring the concentrations of TNF-serum, IL-1 serum, IL-6, hs-CRP, ICAM-1 and MCP-1 in serum by an ELISA method;

3.2.2 detection of vascular endothelial active substance and fibrinolysis system: measuring the content of NO in serum by a nitrate reductase method, and detecting the levels of ET-1, PGI2, TXA2 in serum and PAI-1 and t-PA in plasma by an ELISA method

3.3 statistical treatment

Statistical analysis is carried out on the obtained data by adopting SPSS22.0 software, and the data is measuredThe results are shown in the following table, wherein the comparison among the groups is carried out by adopting one-factor analysis of variance, and the analysis between the two groups is carried out by adopting an independent sample T test mode. With P<A difference of 0.05 is statistically significant.

4. Results and conclusions

4.1 electrocardiographic ST-segment changes of coronary heart disease rat

Compared with the blank group, the electrocardiogram ST segment of each group of rats before modeling is basically not different; after modeling, the ST segment of the rat electrocardiogram is obviously too high, and the ST segment change of the model group is over 0.15mV, thus prompting the success of modeling of the coronary heart disease.

Compared with the model group, the electrocardiogram ST segment of the rats of each administration group is higher and smaller, and the difference has statistical significance (P is less than 0.05 or P is less than 0.01), wherein the electrocardiogram change of the high and medium dose groups of the embodiment 2 is equivalent to that of the astragalus-ginseng qi-tonifying dropping pill group.

TABLE 4 comparison of ECG data of rats in each group: (n＝10)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

4.2 coronary heart disease rat inflammatory factor changes

Compared with the blank group, the TNF-alpha, IL-1, IL-6, hs-CRP, MCP-1 and ICAM-1 of the rats in other groups are obviously increased, which indicates that the model-making rats have obvious inflammatory reaction.

Compared with the model group, the inflammatory factors of rats in each administration group are reduced to different degrees (P is less than 0.05 or P is less than 0.01), and the high and medium dose groups in example 2 are reduced most obviously and are equivalent to the qi-tonifying dripping pill group of astragalus and ginseng.

TABLE 5 comparison of inflammatory factors in rats of various groups: (n＝10，pg/ml)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

4.3 coronary artery disease rat vascular endothelial active substance changes

Compared with the blank group, the ET-1 and TXA2 of the rats in other groups are obviously increased, and NO and PGI2 are obviously reduced, which shows that the vascular dilation effect and the vascular constriction effect of the model rats are weakened.

Compared with the model group, the rats ET-1 and TXA2 in each administration group are obviously reduced, NO and PGI2 are obviously increased (P is less than 0.05 or P is less than 0.01), and the change of the high and medium dose group in example 2 is most obvious and is equivalent to that of the astragalus-ginseng qi-tonifying dropping pill group.

TABLE 6 comparison of vascular endothelial active substance in rats of various groups: (n＝10)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

4.4 coronary heart disease rat fibrinolytic System Change

Compared with the blank group, t-PA of rats in other groups is obviously reduced, PAI-1 is obviously increased, and the reduction of fibrinolysis function and the enhancement of blood coagulation function of model rats are suggested.

Compared with the model group, the t-PA of rats in each administration group is increased, the PAI-1 is reduced (P is less than 0.01), and the high and medium dose groups in example 2 have the most obvious change and are equivalent to the qi-tonifying dripping pill group of astragalus and ginseng.

TABLE 7 comparison of changes in fibrinolytic System in rats of various groups: (n＝10，ng/ml)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

secondly, the traditional Chinese medicine composition has the treatment effect on ischemia reperfusion injury of rats with coronary heart disease

1 Material

1.1 animals:

wister rat, SPF grade, 180-: SYXK (lu) 20180008, provided by lumnan pharmaceutical group ltd, was acclimatized for one week prior to the experiment.

1.2 drugs, reagents

1.2.1 medicaments

Formulations obtained in examples 2, 3 and 5 of the invention

1.2.3 dosage

Example 2 granules: 1.9g/kg (low dose), 2.7g/kg (medium dose), 5.4g/kg (high dose)

Example 3 granules: 2.7g/kg

Example 5 capsule contents: 0.9g/kg

2. Modeling, grouping and administering drugs

80 rats were randomly divided into a sham operation group, a model group, 3 dose groups of example 2 (high, medium, low), an example 3 group, and an example 5 group. Except for the sham operation group and the model group, rats in each group were gavaged with the corresponding drug for 7 consecutive days.

1h after the end of the last administration, a surgical procedure was performed: the rat is anesthetized, fixed on an operating table for thoracotomy, the heart is exposed, the left anterior descending branch of the coronary artery of the rat is ligated, after 2h of ligation, the ligation line is loosened, reperfusion is carried out for 2h, and a myocardial ischemia reperfusion model is established.

The sham group was operated only without ligation, and the remaining groups were operated as described above.

After the model is successfully established, detecting relevant indexes of rats.

3 observation index

3.1 detection of myocardial infarction area: after 2h of reperfusion, the rats were sacrificed, the heart was dissected away, and the myocardial infarction area was measured.

3.2 determination of myocardial Tri-enzyme: after 2h of reperfusion, blood was taken from the abdominal aorta of the rat, serum was centrifuged, and creatine kinase isoenzyme (CK-MB), aspartate Aminotransferase (AST), and Lactate Dehydrogenase (LDH) activities in the serum were measured according to the kit instructions.

3.3 determination of oxidative stress indicators in myocardial tissues: after blood collection is finished, myocardial tissue homogenate is prepared from myocardial tissue in the heart of a rat, and the activity of superoxide dismutase (SOD), Catalase (CAT) and glutathione peroxidase (GSH-px) and the content of Malondialdehyde (MDA) in the myocardial tissue are detected according to a kit instruction method.

3.4 statistical treatment

Statistical analysis is carried out on the obtained data by adopting SPSS22.0 software, and the data is measuredThe results are shown in the following table, wherein the comparison among the groups is carried out by adopting one-factor analysis of variance, and the analysis between the two groups is carried out by adopting an independent sample T test mode. With P<A difference of 0.05 is statistically significant.

4. Results and conclusions

4.1 comparison of myocardial infarction status in rats

Rats in each of the remaining groups experienced different degrees of myocardial infarction (P < 0.01) compared to sham operated groups.

Compared with the model group, the myocardial infarction area of rats in each administration group is obviously reduced (P < 0.01), wherein the myocardial infarction area of the rats in the high and medium dose groups of the embodiment 2 is the lowest.

TABLE 8 comparison of myocardial infarct size in rats of various groups: (n＝10)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

4.2 comparison of myocardial Tri-enzyme changes in rats

Compared with the sham operation group, the CK-MB, AST and LDH activities of the rats in the other groups are obviously improved (P is less than 0.05 or P is less than 0.01).

Compared with the model group, the CK-MB, AST and LDH activities of rats in each administration group are obviously reduced (P is less than 0.01), and the reduction is most obvious in the high and medium dose groups of the embodiment 2.

TABLE 9 comparison of myocardial triszyme changes in rats of various groups: (n＝10)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。

4.3 oxidative stress index changes in rat myocardial tissue

Compared with the sham operation group, the MDA content of rats in other groups is obviously increased, and the activities of SOD, CAT and GSH-px are obviously reduced (P is less than 0.05 or P is less than 0.01).

Compared with the model group, the rats with MDA content of each administration group are obviously reduced, the activities of SOD, CAT and GSH-px are obviously improved (P is less than 0.05 or P is less than 0.01), and the change is most obvious in the high and medium dose groups of the embodiment 2.

TABLE 10 comparison of myocardial tissue oxidative stress index changes in rats of various groups: (n＝10)

Note: in contrast to the blank group,^@P＜0.05，*P＜0.01；

in contrast to the model set,^△P＜0.05，^#P＜0.01。