Traditional Chinese medicine compound preparation for treating coronary heart disease with depression and application thereof

Abstract

The invention discloses a traditional Chinese medicine compound preparation for treating coronary heart disease with depression and application of the traditional Chinese medicine compound preparation. The traditional Chinese medicine compound preparation is prepared from radix astragali preparata, honeysuckle flowers, radix scrophulariae, radix salviae miltiorrhizae, rhizoma chuanxiong, flos carthami, fried radix angelicae sinensis, rhizoma polygoni cuspidati, hypericum perforatum, radix curcumae, fried pericarpium citri reticulatae, agilawood and raw radix glycyrrhizae. The invention also discloses application of the traditional Chinese medicine compound preparation in preparation of medicines for treating coronary heart disease with depression. The traditional Chinese medicine compound preparation has the effects of activating blood, detoxifying and relieving depression, effectively relieves angina pectoris, anxiety, depression and coronary heart disease PCI postoperative adverse events caused by coronary heart disease accompanied by depression and traditional Chinese medicine syndrome indexes of coronary heart disease accompanied by depression, promotes blood circulation, relieves depression symptoms and has high popularization and application value.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compound preparations, and specifically to a traditional Chinese medicine compound preparation for treating coronary heart disease with depression and its application. Background Art

[0002] Coronary heart disease combined with depression, as a common dual-heart disease in clinical practice, has an incidence rate as high as 51% in China, among which 0.5% - 25.44% is severe depression. Currently, traditional means are used to intervene in the physical symptoms caused by coronary heart disease in clinical practice, such as chemical drug treatment, percutaneous coronary intervention (PCI), coronary artery bypass grafting, etc. For patients with coronary heart disease combined with depression, antidepressant treatment, psychological intervention, etc. are carried out simultaneously. However, there are the following intractable problems: on the one hand, patients after PCI often have increased psychological pressure, which exacerbates depression and makes the disease more complex; on the other hand, antidepressants can cause various cardiovascular-related adverse reactions. The condition of coronary heart disease with depression is complex and difficult to treat.

[0003] Previous large-sample clinical studies by the team found that coronary heart disease combined with depression presents the characteristic of "mutual binding of stasis, toxin and depression" on the basis of deficiency of healthy qi, and a traditional Chinese medicine compound preparation with the effects of removing stasis, detoxifying and relieving depression was constructed. Through multi-center, randomized, double-blind, placebo parallel controlled clinical trials, it was found that this preparation can improve the integral of traditional Chinese medicine syndromes, angina pectoris, physical limitation and attack frequency, anti-depression and anxiety, improve sleep, etc. of patients, improve the treatment satisfaction and has good safety. Further experimental studies confirmed that it can effectively relieve cardiac remodeling and inflammatory response, and has good clinical efficacy and application value. Summary of the Invention

[0004] In order to solve the certain degree of adverse reactions caused by existing western medicine treatments, as well as the unknown risks and high costs required by surgeries, the present invention provides a safe and effective traditional Chinese medicine compound preparation for treating coronary heart disease with depression.

[0005] The technical solution adopted by the present invention is: A traditional Chinese medicine compound preparation for treating coronary heart disease with depression, the traditional Chinese medicine compound preparation comprises the following raw medicinal materials: roasted astragalus root, honeysuckle flower, scrophularia root, salvia root, chuanxiong rhizome, safflower, stir-fried angelica root, polygonum cuspidatum root, hypericum perforatum, turmeric root-tuber, stir-fried tangerine peel, aloeswood, raw licorice root.

[0006] Further, the traditional Chinese medicine compound preparation is composed of the following raw medicinal materials in parts by weight: 25-35 parts of stir-baked Astragalus membranaceus, 12-20 parts of honeysuckle flower, 10-15 parts of Scrophularia ningpoensis, 12-20 parts of Salvia miltiorrhiza, 8-15 parts of Ligusticum wallichii, 5-10 parts of Carthamus tinctorius, 8-15 parts of stir-fried Angelica sinensis, 12-20 parts of Polygonum cuspidatum root, 1-5 parts of Hypericum perforatum, 8-15 parts of Curcuma aromatica, 5-10 parts of stir-fried Citrus reticulata Blanco, 5-10 parts of Aquilaria sinensis, and 5-10 parts of raw Glycyrrhiza uralensis Fisch.

[0007] More preferably, the traditional Chinese medicine compound preparation is composed of the following raw medicinal materials in parts by weight: 28-32 parts of stir-baked Astragalus membranaceus, 14-16 parts of honeysuckle flower, 10-14 parts of Scrophularia ningpoensis, 14-16 parts of Salvia miltiorrhiza, 8-10 parts of Ligusticum wallichii, 5-7 parts of Carthamus tinctorius, 8-12 parts of stir-fried Angelica sinensis, 14-16 parts of Polygonum cuspidatum root, 2-4 parts of Hypericum perforatum, 8-12 parts of Curcuma aromatica, 5-7 parts of stir-fried Citrus reticulata Blanco, 5-7 parts of Aquilaria sinensis, and 5-7 parts of raw Glycyrrhiza uralensis Fisch.

[0008] More preferably, the traditional Chinese medicine compound preparation is composed of the following raw medicinal materials in parts by weight: 30 parts of stir-baked Astragalus membranaceus, 15 parts of honeysuckle flower, 12 parts of Scrophularia ningpoensis, 15 parts of Salvia miltiorrhiza, 9 parts of Ligusticum wallichii, 6 parts of Carthamus tinctorius, 10 parts of stir-fried Angelica sinensis, 15 parts of Polygonum cuspidatum root, 3 parts of Hypericum perforatum, 10 parts of Curcuma aromatica, 6 parts of stir-fried Citrus reticulata Blanco, 6 parts of Aquilaria sinensis, and 6 parts of raw Glycyrrhiza uralensis Fisch.

[0009] In the present invention, the dosage forms of the traditional Chinese medicine compound preparation include tablets, capsules, granules, dripping pills, pellets, decoctions or mixtures. The traditional Chinese medicine compound preparation can be prepared according to the conventional processes of pharmacy and pharmaceutically acceptable excipients for human body.

[0010] When the traditional Chinese medicine compound preparation is a granule, it can be prepared by the following method: Take stir-baked Astragalus membranaceus, honeysuckle flower, Scrophularia ningpoensis, Salvia miltiorrhiza, Ligusticum wallichii, Carthamus tinctorius, stir-fried Angelica sinensis, Polygonum cuspidatum root, Hypericum perforatum, Curcuma aromatica, stir-fried Citrus reticulata Blanco, and raw Glycyrrhiza uralensis Fisch. Decoct the above twelve herbs twice with water. For the first time, use 10 times the amount of water and decoct for 30-60 minutes. For the second time, use 12 times the amount of water and decoct for 6-8 hours. Filter and combine the decoction liquids, concentrate into an extract, and the extraction rate of the dry extract is 24%-49%. The relative density after concentration is 1.08-1.10. Dry and pulverize to obtain a mixed powder. The mixed powder and the Aquilaria sinensis powder are prepared into granules with pharmaceutically acceptable excipients for human body.

[0011] The present invention also provides the application of the traditional Chinese medicine compound preparation in the preparation of a drug for treating coronary heart disease with depression.

[0012] Furthermore, in the above application, the coronary heart disease with depression is coronary heart disease with depression of the type of mutual binding of stasis-toxicity and stasis.

[0013] In clinical practice, the traditional Chinese medicine compound preparation of the present invention can improve the TCM syndrome scores of patients, the condition of angina pectoris, improve physical limitation and attack frequency, antidepressant and anti-anxiety effects, improve sleep, etc.; it can reduce the heart-body ratio and heart-tibia ratio in rats with coronary heart disease accompanied by depression; it can improve the pathological changes of cardiac fibrosis and hippocampal tissue; increase the protein expression levels of cardiac ATP, PGC-1α, hippocampal PSD-95 and BDNF; it can also inhibit the increase in serum CK-MB, serum and cardiac SOD contents, slow down the blood coagulation duration, reduce the platelet aggregation rate, and restore the hemorheological changes.

[0014] The traditional Chinese medicine compound preparation of the present invention can, to a certain extent, improve the characteristic manifestations of coronary heart disease accompanied by depression.

[0015] The formula of the traditional Chinese medicine compound preparation described in the present invention follows the basic principles of TCM syndrome differentiation and treatment. The raw materials are selected and the dosage ratios are determined. Each component can coordinate and promote each other, playing a synergistic effect. This formula is based on the effects of promoting blood circulation, detoxifying, and relieving depression. In the formula, Scrophulariae Radix, Flos Carthami, Polygoni Cuspidati Rhizoma, and Rhizoma Chuanxiong promote blood circulation to remove blood stasis for relieving pain; Salviae Miltiorrhizae Radix, Angelicae Sinensis Radix, and Astragali Radix nourish blood and replenish qi; Hyperici Perforati Herba, Curcumae Radix, Citri Reticulatae Pericarpium, and Aquilariae Lignum relieve qi stagnation. The chest is the place where qi gathers and blood accumulates, and it is the distribution area of the liver meridian. Therefore, in the whole formula, promoting blood circulation to remove blood stasis and nourishing blood are carried out simultaneously to relieve the stabbing pain in the chest; promoting blood circulation and regulating qi are combined to relieve emotional depression and insomnia and dreaminess; at the same time, ascending and descending are taken into account, which can not only promote the ascending of clear yang, but also promote the descending of qi, so as to harmonize qi and blood. Lonicerae Japonicae Flos and Glycyrrhizae Radix clear and detoxify all poisons. They can not only clear the heat caused by the long-term accumulation of tangible pathogenic factors that cannot be resolved, but also activate the stagnant blood left by the damage of pathogenic toxins to the collaterals. Taking qi and blood into account, promoting blood circulation and nourishing blood at the same time. Although it is a representative formula for treating surgical sores and ulcers, it exactly conforms to the pathogenesis and can achieve the effect of treating different diseases with the same therapy.

[0016] The beneficial effects of the present invention are that it has the effects of promoting blood circulation, detoxifying, and relieving depression, can effectively relieve the TCM syndrome scores of patients caused by coronary heart disease accompanied by depression, the condition of angina pectoris, improve physical limitation and attack frequency, antidepressant and anti-anxiety effects, improve sleep, etc., improve the treatment satisfaction and has good safety, and has great popularization and application value. Description of the Drawings

[0017] Figure 1 It is a flowchart for establishing a model of rats with coronary heart disease accompanied by depression.

[0018] Figure 2 It is an electrocardiogram detection chart of rats in the model group before and after modeling. Among them, Figure A is before the operation; Figure B is during ischemia; Figure C is during reperfusion.

[0019] Figure 3Rat heart ultrasound results graphs for the control group, model group, and experimental group. Among them, Graph A is the heart ultrasound result graph; Graph B is the bar graph of heart rate HR levels; Graph C is the bar graph of stroke volume SV levels; Graph D is the bar graph of left ventricular ejection fraction EF levels; Graph E is the bar graph of left ventricular end-systolic diameter LVIDs levels; Graph F is the bar graph of left ventricular shortening fraction FS levels; Graph G is the bar graph of cardiac output CO levels; Graph H is the bar graph of left ventricular end-diastolic diameter LVIDd levels; Note: n = 8. Compared with the control group, * represents P < 0.05, ** represents P < 0.01, **** represents P < 0.0001; Compared with the model group, # represents P < 0.05, ## represents P < 0.01, # represents P < 0.0001.

[0020] Figure 4 Bar graph of the results of the preference for sugar water in rats of each group, n = 8. Compared with the control group, ** represents P <0.01; Compared with the model group, # represents P <0.05.

[0021] Figure 5 Photos of the hair and status of rats in each group. Among them, Graph A is the hair and status of rats in the 1st week; Group B is the hair and status of rats in the 5th week.

[0022] Figure 6 Graphs of the results of body weight, food intake, and body fat index of rats in each group. Among them, Graph A is the comparison graph of the body weight levels of rats in each group; Graph B is the comparison graph of the food intake levels of rats in each group; Graph C is the comparison graph of the body fat index levels of rats in each group; Note: n = 8. Compared with the control group, *P < 0.05, ****P < 0.0001; Compared with the model group, #P < 0.05, #P < 0.0001.

[0023] Figure 7 Graph of the results of the moisture content of feces in rats of each group. n = 8. Compared with the control group, *P < 0.05, ***P < 0.001, ****P < 0.0001; Compared with the model group, #P < 0.05, ##P < 0.01, #P < 0.0001.

[0024] Figure 8 Comparison graph of the grasping force of the four limbs of rats in each group at the 5th week. Note: n = 8. Compared with the control group, ****P < 0.0001. Compared with the model group, #P < 0.0001.

[0025] Figure 9Comparison chart of the anal temperature results of rats in each group, n = 8, compared with the control group, *P < 0.05, **P < 0.01; compared with the model group, ##P < 0.01.

[0026] Figure 10 Results chart of the heart-to-body ratio and heart-to-tibia ratio of rats in each group. Among them, Figure A is the gross photograph of the heart of rats in each group; Figure B is the horizontal bar comparison chart of the heart-to-body ratio of rats in each group; Figure C is the horizontal comparison chart of the heart-to-tibia ratio of rats in each group; Note: n = 6, compared with the control group, *P < 0.05, **P < 0.01; compared with the model group, #P < 0.05 Figure 11 Comparison chart of the ATP content in the hearts of rats in each group. Note: n = 8, compared with the control group, **P < 0.01; compared with the model group, #P < 0.05.

[0027] Figure 12 Comparison chart of the expression levels of PGC-1α protein in the hearts of rats in each group. Among them, Figure A is the protein expression band chart of PGC-1α; Figure B is the horizontal bar comparison chart of the expression levels of PGC-1α protein; Note: n = 4, compared with the control group, **P < 0.01; compared with the model group, #P < 0.05.

[0028] Figure 13 Comparison chart of the hemorheology, four coagulation items and platelet aggregation rate of rats in each group. Among them, Figures A - D are the horizontal comparison charts of the hemorheology levels of rats in each group; Figure E is the horizontal comparison chart of the platelet aggregation rate levels of rats in each group; Figures F - I are the horizontal comparison charts of the four coagulation item levels of rats in each group; Note: n = 6, compared with the control group, **P < 0.01, ****P < 0.0001, ****P < 0.0001; Compared with the model group, #P < 0.05, ##P < 0.01, P < 0.001, #P < 0.0001.

[0029] Figure 14 Results chart of H&E, Masson staining and fibrosis in the hearts of rats in each group. Among them, the magnifications of H&E and Masson staining are 20× and 40× respectively; Figure A is the H&E staining photograph of the hearts of rats in each group; Figure B is the Masson staining photograph of the hearts of rats in each group; Group C is the horizontal comparison chart of the myocardial fibrosis levels of rats; Note: n = 3, compared with the control group, ***P < 0.001; compared with the model group, ##P < 0.01.

[0030] Figure 15 Comparison chart of the SOD levels in the sera and heart tissues of rats in each group. Among them, Figure A is the horizontal comparison chart of the SOD levels in the sera of rats; Group B is the horizontal comparison chart of the SOD levels in the heart tissues of rats.

[0031] Note: n = 6, compared with the control group, *P < 0.05, **P < 0.01; compared with the model group, #P < 0.05.

[0032] Figure 16 It is a comparison chart of the CK-MB levels in the sera of rats in each group; Note: n = 6, compared with the control group, ***P < 0.001; compared with the model group, #P < 0.05.

[0033] Figure 17 It is a photo of the H&E staining results of the hippocampi of rats in each group (20×, 40×).

[0034] Figure 18 It is a result chart of the expression levels of PSD95 and BDNF proteins in the hippocampi of rats in each group. Among them, Figure A is the protein expression band chart of PSD95, Figure B is the protein expression band chart of BDNF, Figure C is the columnar comparison chart of the PSD95 protein expression level, and Figure D is the columnar comparison chart of the BDNF protein expression level; Note: n = 4, compared with the control group, *P < 0.05; compared with the model group, #P < 0.05. Specific implementation manners

[0035] To make the purpose, technical solutions and advantages of the present application clearer, the following will be described in detail with reference to embodiments, but the protection scope of the present invention is not limited thereto.

[0036] Embodiment 1 The formula of the traditional Chinese medicine compound preparation is: roasted Astragalus membranaceus 30 g, honeysuckle 15 g, Scrophularia ningpoensis 12 g, Salvia miltiorrhiza 15 g, stir-fried Angelica sinensis 10 g, Polygonum cuspidatum root 15 g, Hypericum perforatum 3 g, Curcuma aromatica 10 g, stir-fried Citrus reticulata Blanco 6 g, Ligusticum chuanxiong 9 g, safflower 6 g, Aquilaria sinensis 6 g, raw licorice 6 g.

[0037] It is made into granules according to the following method: S1. Take each medicine in the formula except Aquilaria sinensis according to the weight ratio of medicine to water of 1:10, and soak for 60 minutes; S2. Decoct twice. The first decoction is for 0.5 hour, and the second decoction adds 12 times the amount of water and decocts for 7 hours. Filter and combine the filtrates for standby; S3. Concentrate the filtrate into an extract. The extraction rate of the dry extract is 24% - 49%. After concentration, the relative density is 1.08 - 1.10 parts / ml, and dry it; put it into a pulverizer for pulverization, and pass through a 100-mesh sieve to obtain a mixed fine powder; S4. Take the Aquilaria sinensis slices according to the formula dosage, dry them and pulverize them, and pass through a 100-mesh sieve to obtain fine Aquilaria sinensis powder; S5. Mix the fine powder and the fine agarwood powder with excipients maltodextrin and lactose, mix evenly, granulate to obtain the granule agent, with each portion containing 6.5 g of crude drug content. Denote it as HJSSJW granule agent.

[0038] Example 2 (I) Experimental materials 1. Experimental animals Use SPF-grade 8-week-old male SD rats, with a body weight of 200 ± 20 g, at the clean level.

[0039] 2. Experimental drugs Use the granule agent prepared in Example 1 for the experiment. Refer to the method in "Methodology of Traditional Chinese Medicine Pharmacological Research" to convert the equivalent dosage for rats, and administer the drug by gavage. Each portion of the granule agent contains 6.5 g of crude drug content. Add 40 mL of water to obtain the medicinal liquid, and administer the medicinal liquid at a rate of 1 mL per 100 g of body weight according to the rat body weight.

[0040] 3. Main reagents and equipment: glycine, BDNF antibody, PSD 95 antibody, digital pathological section scanning analyzer, rat grip strength tester, open field experiment, tail suspension experiment (II) Experimental methods 1. Animal grouping First, all rats are fed adaptively. After 1 week, they are randomly grouped by body weight into a control group, a model group, and an experimental group, with 10 rats in each group.

[0041] 2. Modeling method The flowchart for establishing the model of rats with coronary heart disease accompanied by depression is as Figure 1 shown. Except for the control group, the other groups are subjected to a 4-week chronic unpredictable mild stress modeling. To avoid the experimental rats adapting to the modeling stimuli, the experimenters randomly select 2 - 3 different stimulation methods every day, and ensure that each method is not continuously used. The stimulation types selected during the experiment include: fasting for 24 h, water deprivation for 24 h, shaking the cage for 15 min, restraint for 4 h, strong light irradiation for 5 min, tilted cage for 24 h, ice water swimming for 5 min, wet bedding for 24 h, tail clamping for 5 min, no bedding for 24 h, and odor stimulation for 24 h. In the 5th week, the rats are subjected to left anterior descending coronary artery ligation, with ischemia for 30 min and reperfusion for 1 week to construct a cardiac ischemia-reperfusion model. Intramuscular injection of atropine, intraperitoneal injection of Zoletil for anesthesia, fix in the supine position, expose the heart, ligate the left anterior descending coronary artery. The whitening of the left ventricular apex and anterior wall indicates cardiac ischemia. After 30 min, releasing the ligation and the change of the left ventricular apex and anterior wall from white to red indicates successful reperfusion.

[0042] 3. Experimental procedures After 1 week of adaptive feeding, the control group and the model group were fed normally and given saline by gavage. While the model was established in the experimental group, the granule prepared in Example 1 was given by gavage, and the experimental rats were designated as the HJSSJW group. Every week, the body weight changes, food intake, changes in fur characteristics, fecal traits and moisture content, anal temperature, mental state and motor state of all experimental rats were observed and recorded. After the model establishment, the grasping force of the four limbs of the rats was measured, and behavioral tests and cardiac ultrasound examinations were carried out. The rats were anesthetized, and blood was collected from the abdominal aorta and stored in an EP tube, mixed well, centrifuged at 3500 rpm for 15 min at 4 °C, and the supernatant was taken and stored in a -80 °C refrigerator for later use. The heart, brain and other tissues of the rats were collected. Part of the tissues were immersed in paraformaldehyde and stored in a 4 °C refrigerator, and the remaining tissues were labeled and stored in a -80 °C refrigerator in separate tubes.

[0043] (III) Experimental Results 1. Indexes Related to Model Evaluation 1.1 Electrocardiogram Detection The electrocardiogram results are as Figure 2 shown. Among them, Figure A is before the operation; Figure B is during ischemia; Figure C is during reperfusion. The results show that compared with before ischemia, the ST segment of the electrocardiogram showed varying degrees of elevation when the left anterior descending branch of the rat was ligated, indicating that the rat's heart was in the ischemic stage. 30 minutes later, when reperfusion was performed on the rat, the electrocardiogram showed varying degrees of decrease in the ST segment, indicating the reperfusion stage.

[0044] 1.2 Cardiac Function Detection The cardiac ultrasound results are as Figure 3 shown. Among them, Figure A is the cardiac ultrasound result diagram; Figure B is the bar chart of the heart rate HR level; Figure C is the bar chart of the stroke volume SV level; Figure D is the bar chart of the left ventricular ejection fraction EF level; Figure E is the bar chart of the left ventricular end-systolic diameter LVIDs level; Figure F is the bar chart of the left ventricular shortening fraction FS level; Figure G is the bar chart of the cardiac output CO level; Figure H is the bar chart of the left ventricular end-diastolic diameter LVIDd level. The results show that compared with the control group, the SV, EF, FS, and CO of the rats in the model group decreased significantly (P < 0.05, P < 0.0001, P < 0.01, P < 0.01), and the HR, LVIDd, and LVIDs increased significantly (P < 0.0001, P < 0.01, P < 0.05), indicating the deterioration of cardiac function; compared with the model group, in the HJSSJW group of rats, the EF and FS increased significantly (P < 0.01, P < 0.05), the HR and LVIDd decreased significantly (P < 0.0001, P < 0.05), and the LVIDs, CO, and SV all decreased but there was no statistical difference (P > 0.05), indicating the recovery of cardiac function.

[0045] 1.3 Detection of Sucrose Preference The graph of the detection results of sucrose preference is as follows Figure 4 shown. The results show that compared with the control group, the preference of rats in the model group for ingesting sucrose decreased significantly (P < 0.01). After administration of HJSSJW granules, the degree of preference of rats for sucrose increased significantly (P < 0.05).

[0046] 2. Evaluation indicators for the characteristics of pathogenesis factors 2.1. Indexes related to qi deficiency 2.1.1 State of rats The photos of the hair and state of rats in each group are as follows Figure 5 shown. Among them, Figure A shows the hair and state of rats in the first week; Group B shows the hair and state of rats in the fifth week. The results show that before the start of modeling, the hair of rats in each group was bright and shiny and their mental state was full. When caught by the experimenters, they were sensitive in response, active in performance, and struggled violently. As the modeling process continued, the rats in the model group gradually showed a listless state, accompanied by messy hair, yellowing of the hair color, gradually losing resistance to stimuli and the experimenters, and taking a longer time to recover from the stimuli; after intervention with HJSSJW granules, the mental state of the rats recovered, the hair was smoother than that of the model group, and they had strong resistance behaviors to stimuli and could recover quickly after the stimuli ended.

[0047] 2.1.2 Body weight and food intake The graphs of the body weight, food intake, and body fat index of rats in each group are as follows Figure 6 shown. Among them, Figure A is the comparison graph of the body weight levels of rats in each group; Figure B is the comparison graph of the food intake levels of rats in each group; Figure C is the comparison graph of the body fat index levels of rats in each group.

[0048] The results show that during the 1-week adaptive feeding stage before the start of modeling, there was no significant difference in the body weight of rats in each group. One week after modeling, compared with the control group, the body weight of the model group had shown a significant downward trend (P < 0.0001). During the subsequent modeling period, although the body weight of the rats in the model group increased, it increased more slowly than that of the normal group. By the fifth week, the body weight of the model group had shown a significant decrease compared with the control group (P < 0.0001); compared with the model group, the body weight of the rats in the HJSSJW group increased faster and was significantly higher than that of the model group at the fifth week (P < 0.0001) ( Figure 6 in Figure A).

[0049] During the 1-week adaptive feeding stage before the start of model establishment, there were no significant differences in the food intake of rats in each group. Since the 3rd week of model establishment, the food intake of the model rats began to decline. By the 5th week, the food intake of the rats in the model group showed a significant decrease compared with that of the control group (P < 0.0001); compared with the model group, the food intake of the rats in the HJSSJW group increased steadily. At the 5th week, the food intake of the rats in the HJSSJW group was significantly higher than that of the model group (P < 0.0001) ( Figure 6 Figure B).

[0050] The f value of the body fat coefficient showed that compared with the control group, the rats in the model group were significantly emaciated (P < 0.05); after administration of HJSSJW, although the body shape of the rats recovered to a certain extent, there was no statistical difference (P > 0.05) ( Figure 6 Figure C).

[0051] 2.1.3 Fecal moisture content The results of the fecal moisture content of rats in each group are shown as Figure 7 follows. The results showed that in the 2nd week of model establishment, the fecal moisture content of the rats in the model group was already higher than that of the control group (P < 0.05). During the subsequent model establishment process, the fecal moisture content of the rats in the model group gradually increased. At the 5th week, the fecal moisture content of the model group was significantly higher than that of the control group (P < 0.0001); after intragastric administration of traditional Chinese medicine in the HJSSJW group, the fecal moisture content showed a recovery state compared with the model group (P < 0.05).

[0052] 2.1.4 Determination of the grasping force of the four limbs The comparison chart of the grasping force of the four limbs of rats in each group at the 5th week is shown as Figure 8 follows. The grasping force of rats in each group increased during the experiment. After the model establishment, compared with the control group, the grasping force of the rats in the model group decreased significantly (P < 0.0001); compared with the model group, the grasping force of the rats in the HJSSJW group was significantly higher than that of the model group (P < 0.0001).

[0053] 2.1.5 Rectal temperature measurement The rectal temperature results of rats in each group are shown as Figure 9 follows. Compared with the control group, the rectal temperature of the mice in the model group showed no obvious change in the first 3 weeks. Since the 4th week, there was a downward trend, and it was significantly lower than that of the control group at the 5th week (P < 0.01); compared with the model group, although the change in the rectal temperature of the rats in the HJSSJW group was not statistically significant, there was a slightly upward trend (P > 0.05).

[0054] 2.1.6 Heart-body ratio and heart-tibia ratio The results of the heart-body ratio and heart-tibia ratio of rats in each group are shown as Figure 10As shown in the figure, where Figure A is the gross photograph of the hearts of rats in each group; Figure B is the horizontal bar comparison chart of the heart / body ratio of rats in each group; Figure C is the horizontal comparison chart of the heart / tibia ratio of rats in each group. The results showed that compared with the control group, the heart / body ratio and heart / tibia ratio of rats in the model group were significantly increased (P < 0.01, P < 0.05); after treatment with HJSSJW granules, the heart / body ratio of rats was significantly decreased (P < 0.05), and there was also a downward trend in the heart / tibia ratio, but there was no statistical difference (P > 0.05).

[0055] 2.1.7 Effect on cardiac ATP The results of the ATP levels in the cardiac tissues of rats in each group are shown in the following table and Figure 11 as shown. Compared with the control group, the ATP level in the cardiac tissues of rats in the model group was significantly decreased (P < 0.01); compared with the model group, after intragastric administration of HJSSJW granules, the ATP level in the cardiac tissues was increased (P < 0.05) (Table 10, Figure 11 ).

[0056] ATP levels in the cardiac tissues of rats in each group (nmol / mg) (Mean ± SD, n = 8) Control group Model group HJSSJW 16.11±2.48 <![CDATA[10.44±1.23 ** > <![CDATA[14.69±2.99 # > 2.1.8 Expression level of cardiac PGC-1α protein The results of the expression levels of PGC-1α protein in the cardiac tissues of rats in each group are as Figure 12 shown. Among them, Figure A is the protein expression band diagram of PGC-1α; Figure B is the horizontal bar comparison chart of the PGC-1α protein expression level. The results showed that compared with the control group, the expression level of PGC-1α protein in the cardiac tissues of rats in the model group was significantly decreased (P < 0.01). Compared with the model group, after intragastric administration of HJSSJW granules, the level of PGC-1α protein in the cardiac tissues was increased (P < 0.05). ( Figure 12 ) 2.1.9 Biochemical indexes The results of hemorheology, four coagulation indexes and platelet aggregation rate of rats in each group are as Figure 13 shown. Among them, Figures A - D are the horizontal comparison charts of hemorheology levels of rats in each group; Figure E is the horizontal comparison chart of platelet aggregation rate levels of rats in each group; Figures F - I are the horizontal comparison charts of four coagulation indexes of rats in each group.

[0057] The results showed that compared with the control group, the low shear, medium shear, high shear levels and Casson viscosity of hemorheology in the model group rats all increased to varying degrees (P < 0.0001, P < 0.0001, P < 0.001, P < 0.001), the coagulation time of FIB, APTT, TT, PT was significantly shortened (P < 0.01, P < 0.0001, P < 0.0001, P < 0.01), and the platelet aggregation rate increased significantly (P < 0.01); compared with the model group, after administration of HJSSJW granules, the low shear, medium shear, high shear levels and Casson viscosity of hemorheology could be down-regulated (P < 0.001, P < 0.0001, P < 0.01, P < 0.05), the coagulation time of FIB, APTT, TT was prolonged (P < 0.05, P < 0.01, P < 0.05), although PT was prolonged, the difference was not statistically significant (P > 0.05), and the platelet aggregation rate decreased, but the difference was not statistically significant (P > 0.05).

[0058] 2.2.0 Pathological staining The H&E, Masson staining and fibrosis results of the hearts of rats in each group are as Figure 14 shown, where the H&E and Masson stainings are 20× and 40× respectively; Figure A is the H&E staining photo of the hearts of rats in each group; Figure B is the Masson staining photo of the hearts of rats in each group; Figure C is the comparison chart of the myocardial fibrosis levels of rats.

[0059] The results of H&E staining showed that the cardiac structure of the control group rats was normal, and the tissue was arranged neatly and tightly. The overall structure of the myocardium of the model group rats was disordered, and the myocardial space was widened. The morphological structure of the myocardial tissue of the HJSSJW group rats was greatly improved compared with the model group, and the myocardial space was alleviated to a certain extent ( Figure 14 Figure A).

[0060] The results of Masson staining showed that there was no collagen fiber deposition in the control group; compared with the normal group, the collagen fiber deposition in the damaged area of the model group was severe (P < 0.001); after the intervention of HJSSJW granules, the degree of myocardial fibrosis decreased significantly (P < 0.01) ( Figure 14 Figure B).

[0061] 2.2.1 Detection of superoxide dismutase (SOD) in serum and heart tissue The results of SOD levels in the serum and heart tissue of rats in each group are as Figure 15As shown in the figure, Figure A is the comparison chart of SOD levels in rat serum; Figure B is the comparison chart of SOD levels in rat heart tissue. The results showed that compared with the control group, the SOD levels in the serum and heart tissue of the model group rats decreased significantly (P < 0.01, P < 0.05); compared with the model group, after administration of HJSSJW granules, the SOD levels in the serum and heart tissue were significantly up-regulated (P < 0.05, P < 0.05).

[0062] 2.2.2 Detection of CK-MB in serum The results of CK-MB levels in the serum of rats in each group were as Figure 16 shown. Compared with the control group, the CK-MB level in the serum of the model group rats increased significantly (P < 0.001); compared with the model group, the CK-MB in the serum of the HJSSJW group decreased significantly (P < 0.05).

[0063] 2.2.3 Pathological examination The results of H&E staining of the hippocampus of rats in each group were as Figure 17 shown. The results of H&E staining showed that the structure of the DG area of the hippocampal tissue of the control group rats was intact, the cell morphology was regular, and the arrangement was tight and orderly; compared with the control group, the structure of the DG area of the hippocampal tissue of the model group was disordered, the cell arrangement was loose and irregular, and some cells showed karyopyknosis and vacuolar degeneration. The degree of degeneration and injury of the DG area of the hippocampal tissue in the HJSSJW group was less, the cell structure was more complete, and the arrangement order was more regular and tight.

[0064] 2.2.4 Effects on the expression levels of PSD95 and BDNF proteins in the hippocampus The results of the expression levels of PSD95 and BDNF proteins in the hippocampus of rats in each group were as Figure 18 shown. Among them, Figure A is the protein expression band diagram of PSD95, Figure B is the protein expression band diagram of BDNF, Figure C is the columnar comparison diagram of the PSD95 protein expression level, and Figure D is the columnar comparison diagram of the BDNF protein expression level.

[0065] The results showed that compared with the control group, the expression levels of PSD95 and BDNF proteins in the hippocampal tissue of the model group rats decreased significantly (P < 0.05, P < 0.05). Compared with the model group, after intragastric administration of traditional Chinese medicine of HJSSJW granules, the levels of PSD95 and BDNF proteins in the hippocampal tissue increased (P < 0.05).

[0066] Conclusion The present invention comprehensively evaluated rats with coronary heart disease accompanied by depression from the aspects of apparent indexes, pathological indexes and biochemical indexes. It was found that the traditional Chinese medicine compound preparation of the present invention could reduce the heart-body ratio and heart-tibia ratio in rats with coronary heart disease accompanied by depression; improve the pathological changes of cardiac fibrosis and hippocampal tissue; increase the protein expression levels of cardiac ATP, PGC-1α, hippocampal PSD-95 and BDNF. HJSSJW granules could also inhibit the increase in serum CK-MB, serum and cardiac SOD contents, slow down the blood coagulation time, reduce the platelet aggregation rate, and restore the hemorheological changes. In summary, HJSSJW granules can improve the characteristic manifestations of coronary heart disease accompanied by depression in rats to a certain extent.

Claims

1. A Chinese medicinal compound preparation for treating coronary heart disease with depression, characterized in that The Chinese medicine compound preparation comprises the following raw materials: roasted astragalus, honeysuckle, Scrophularia, Salvia, Chuanxiong, safflower, stir-fried angelica, Polygonum cuspidatum root, St. John's wort, Curcuma, stir-fried tangerine peel, agarwood, and raw licorice.

2. The Chinese medicinal compound preparation for treating coronary heart disease with depression as claimed in claim 1, characterized in that The Chinese medicine compound preparation is composed of the following raw materials in parts by weight: 25-35 parts of roasted astragalus, 12-20 parts of honeysuckle, 10-15 parts of Scrophularia, 12-20 parts of Salvia, 8-15 parts of Chuanxiong, 5-10 parts of safflower, 8-15 parts of stir-fried angelica, 12-20 parts of Polygonum cuspidatum root, 1-5 parts of St. John's wort, 8-15 parts of Curcuma, 5-10 parts of stir-fried tangerine peel, 5-10 parts of agarwood, and 5-10 parts of raw licorice.

3. The Chinese medicinal compound preparation for treating coronary heart disease with depression as claimed in claim 1, characterized in that The Chinese medicine compound preparation is composed of the following raw materials in parts by weight: 28-32 parts of roasted astragalus, 14-16 parts of honeysuckle, 10-14 parts of Scrophularia, 14-16 parts of Salvia, 8-10 parts of Chuanxiong, 5-7 parts of safflower, 8-12 parts of stir-fried angelica, 14-16 parts of Polygonum cuspidatum root, 2-4 parts of St. John's wort, 8-12 parts of curcuma, 5-7 parts of stir-fried tangerine peel, 5-7 parts of agarwood, and 5-7 parts of raw licorice.

4. The Chinese medicinal compound preparation for treating coronary heart disease with depression as claimed in claim 1, characterized in that The Chinese medicine compound preparation is composed of the following raw materials in parts by weight: 30 parts of roasted astragalus, 15 parts of honeysuckle, 12 parts of Scrophularia, 15 parts of Salvia, 9 parts of Chuanxiong, 6 parts of safflower, 10 parts of stir-fried angelica, 15 parts of Polygonum cuspidatum root, 3 parts of St. John's wort, 10 parts of Curcuma, 6 parts of stir-fried tangerine peel, 6 parts of agarwood, and 6 parts of raw licorice.

5. The Chinese medicinal compound preparation according to claim 1, characterized in that The dosage forms of the Chinese medicine compound preparation include tablets, capsules, granules, dripping pills, micropills, decoctions or mixtures.

6. The Chinese medicinal compound preparation according to claim 5, characterized in that When the Chinese medicine compound preparation is a granule, it is prepared by the following method: Take roasted astragalus, honeysuckle, Scrophularia, Salvia miltiorrhiza, Chuanxiong, safflower, stir-fried angelica, Polygonum cuspidatum root, St. John's wort, Curcuma, stir-fried tangerine peel, and raw licorice, add water and boil twice, the first time with 10 times the amount of water, boil for 30-60 minutes, the second time with 12 times the amount of water, boil for 6-8 hours, filter and combine the medicinal liquids, concentrate into extract, the dry extract yield is 24%-49%, and the relative density after concentration is 1.08-1.

10. After drying and crushing, a mixed powder is obtained, and the mixed powder and agarwood powder are mixed with pharmaceutical excipients acceptable to the human body to prepare granules.

7. Use of the Chinese medicinal compound preparation according to any one of claims 1 to 6 in the preparation of a medicament for treating coronary heart disease with depression.

8. The use according to claim 7, characterized in that The coronary heart disease with depression is coronary heart disease with depression of the blood stasis, toxicity and depression type.

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