Application of Danshu Fuyuan Recipe in the preparation of drugs for the treatment of coronary heart disease

Abstract

The present invention belongs to the field of pharmaceuticals, and specifically relates to the application of Danshu Fuyuan Formula in the preparation of drugs for treating coronary heart disease. The Danshu Fuyuan Formula comprises the following raw materials in parts by weight: 25 - 35 parts of Salvia miltiorrhiza, 10 - 15 parts of Atractylodes macrocephala, 25 - 35 parts of Astragalus membranaceus, 10 - 20 parts of Lonicera japonica, 10 - 20 parts of Polygonum cuspidatum, 10 - 20 parts of Curcuma aromatica, 10 - 15 parts of Poria cocos, 25 - 35 parts of Coix lacryma-jobi, and 10 - 15 parts of Notopterygium incisum. Research shows that the Danshu Fuyuan Formula of the present invention can regulate the levels of four blood lipids in rats with coronary heart disease, and the Danshu Fuyuan Formula at high dose has a stronger ability to regulate blood lipids; in addition, the Danshu Fuyuan Formula can inhibit the secretion of serum inflammatory factors and the expression of inflammatory proteins; and the Danshu Fuyuan Formula may play a therapeutic role on rats with coronary heart disease by inhibiting the TLR4 / NF-κB pathway. The Danshu Fuyuan Formula of the present invention provides a new idea for the treatment of coronary heart disease.

Description

Technical Field

[0001] The present invention belongs to the field of drugs, and particularly relates to the application of Danshu Fuyuan Prescription in the preparation of drugs for treating coronary heart disease. Background Art

[0002] Coronary heart disease, also known as coronary atherosclerotic heart disease, refers to heart disease caused by myocardial ischemia and hypoxia due to coronary atherosclerosis. The coronary artery is the only blood vessel that supplies blood to the heart, and its shape resembles a crown, so it is called the coronary artery. When the coronary artery hardens and shows atherosclerotic changes, it will cause obstacles to the blood circulation supplying the heart, resulting in myocardial ischemia and hypoxia, and in severe cases, it can endanger life.

[0003] Existing drugs for treating coronary heart disease mainly include: nitrate preparations, β-blockers, calcium antagonists, lipid-lowering drugs, anticoagulants and antiplatelet drugs, etc. Taking western medicine will cause a certain degree of damage to the liver. And coronary heart disease mostly occurs in the elderly. How to treat the disease without increasing the additional physical burden on the elderly is the research focus in the field of drugs.

[0004] Therefore, based on this, the technical solution of the present invention is proposed. Summary of the Invention

[0005] In order to solve the problems existing in the prior art, the solution of the present invention is to provide the application of Danshu Fuyuan Prescription in the preparation of drugs for treating coronary heart disease. The raw materials of the Danshu Fuyuan Prescription include: Salvia miltiorrhiza, Atractylodes macrocephala, Astragalus membranaceus, Lonicera japonica, Polygonum cuspidatum, Curcuma aromatica, Poria cocos, Coix lacryma-jobi, and Notopterygium incisum.

[0006] In the prescription, Salvia miltiorrhiza is bitter and slightly cold in nature, enters the pericardium and liver meridians, has the same efficacy as the four drugs of Siwu Decoction, and has the effect of cooling blood and promoting blood circulation. It is the monarch drug of this prescription; Atractylodes macrocephala and Astragalus membranaceus are used as ministers to supplement vital energy. Lonicera japonica and Polygonum cuspidatum clear the heat in the blood vessels and disperse the formed nodules; Poria cocos and Coix lacryma-jobi are used as assistants to strengthen the spleen and resolve phlegm, and also make Astragalus membranaceus and Atractylodes macrocephala tonify without causing stagnation; Curcuma aromatica combined with Lonicera japonica and Polygonum cuspidatum helps Salvia miltiorrhiza clear heat, cool blood and disperse nodules; Notopterygium incisum is used as an assistant and guide. On the one hand, by virtue of its pungent and warm nature, the whole prescription is not overly cold. On the other hand, with the ascending and clearing power of the wind drug, it promotes the rising of yang qi, and combined with Astragalus membranaceus and Atractylodes macrocephala, it restores the ascending and descending of the qi mechanism of the spleen and stomach. The whole prescription combines cold and heat, combines attack and supplementation, and the compatibility is scientific and reasonable.

[0007] Preferably, the Danshu Fuyuan Prescription comprises the following raw materials in parts by weight: 25-35 parts of Salvia miltiorrhiza, 10-15 parts of Atractylodes macrocephala, 25-35 parts of Astragalus membranaceus, 10-20 parts of Lonicera japonica, 10-20 parts of Polygonum cuspidatum, 10-20 parts of Curcuma aromatica, 10-15 parts of Poria cocos, 25-35 parts of Coix lacryma-jobi, and 10-15 parts of Notopterygium incisum.

[0008] Preferably, the Danshu Fuyuan Prescription comprises the following raw materials in parts by weight: 30 parts of Salvia miltiorrhiza, 12 parts of Atractylodes macrocephala, 30 parts of Astragalus membranaceus, 15 parts of Lonicera japonica, 15 parts of Polygonum cuspidatum, 15 parts of Curcuma aromatica, 12 parts of Poria cocos, 30 parts of Coix lacryma-jobi, and 12 parts of Notopterygium incisum.

[0009] Preferably, the preparation method of the Danshu Fuyuan formula is as follows:

[0010] Crush the raw materials of the Danshu Fuyuan formula and then mix them to obtain a composition;

[0011] Or, mix the raw materials of the Danshu Fuyuan formula and then crush them to obtain a composition;

[0012] Or, extract and refine the raw materials of the Danshu Fuyuan formula according to conventional processes to obtain one of tablets, capsules, granules, pills, powders or oral liquids.

[0013] Preferably, the drug is a drug for improving the myocardial enzyme level of coronary heart disease.

[0014] Preferably, the drug is a drug for improving the cardiac function of coronary heart disease.

[0015] Preferably, the drug is a drug for improving the myocardial ischemia state of coronary heart disease.

[0016] Preferably, the drug is a drug for improving the pathological state of coronary heart disease.

[0017] Preferably, the drug is a drug for improving the blood lipid level of coronary heart disease.

[0018] Preferably, the drug is a drug for improving the serum inflammation level of coronary heart disease;

[0019] And / or, the drug is a drug for improving the mRNA transcription of myocardial tissue in coronary heart disease;

[0020] And / or, the drug is a drug for improving the expression of inflammatory proteins in myocardial tissue of coronary heart disease;

[0021] And / or, the drug is a drug for improving the expression of pathway proteins in myocardial tissue of coronary heart disease.

[0022] The beneficial effects of the present invention are as follows:

[0023] Studies have shown that the Danshu Fuyuan formula of the present invention can regulate the levels of four blood lipids in rats with coronary heart disease, and the Danshu Fuyuan formula at high doses has a stronger ability to regulate blood lipids; in addition, the Danshu Fuyuan formula can inhibit the secretion of serum inflammatory factors and the expression of inflammatory proteins; and the Danshu Fuyuan formula may play a therapeutic role in rats with coronary heart disease by inhibiting the TLR4 / NF-κB pathway. The Danshu Fuyuan formula of the present invention provides a new idea for the treatment of coronary heart disease. Description of the Drawings

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the accompanying drawings required for the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can be obtained based on these drawings.

[0025] Figure 1 It is the detection result diagram of CK-MB in the serum of rats in each group.

[0026] Figure 2 It is the detection result diagram of the activity of LDH in the serum of rats in each group.

[0027] Figure 3 It is the planar detection diagram of the heart ultrasound of the rats in the sham operation group.

[0028] Figure 4 It is the planar detection diagram of the heart ultrasound of the rats in the model group.

[0029] Figure 5 It is the planar detection diagram of the heart ultrasound of the rats in the low-dose group.

[0030] Figure 6 It is the planar detection diagram of the heart ultrasound of the rats in the medium-dose group.

[0031] Figure 7 It is the planar detection diagram of the heart ultrasound of the rats in the high-dose group.

[0032] Figure 8 It is the planar detection diagram of the heart ultrasound of the rats in the positive drug group.

[0033] Figure 9 It is the detection result diagram of EF of the rats in each group.

[0034] Figure 10 It is the detection result diagram of FS of the rats in each group.

[0035] Figure 11 It is the detection result diagram of IVSd of the rats in each group.

[0036] Figure 12 It is the detection result diagram of IVSs of the rats in each group.

[0037] Figure 13 It is the anatomical diagram of myocardial infarction of the rats in each group.

[0038] Figure 14 It is the diagram of the proportion (area) of myocardial infarction of the rats in each group.

[0039] Figure 15 It is the HE staining result diagram of the myocardial tissue of the rats in the sham operation group (×40).

[0040] Figure 16 It is the HE staining result diagram of the myocardial tissue of the model group rats (×40).

[0041] Figure 17 It is the HE staining result diagram of the myocardial tissue of the low-dose group rats (×40).

[0042] Figure 18 It is the HE staining result diagram of the myocardial tissue of the medium-dose group rats (×40).

[0043] Figure 19 It is the HE staining result diagram of the myocardial tissue of the high-dose group rats (×40).

[0044] Figure 20 It is the HE staining result diagram of the myocardial tissue of the positive drug group rats (×40).

[0045] Figure 21 It is the Masson staining result diagram of the myocardial tissue of the sham operation group rats (×40).

[0046] Figure 22 It is the Masson staining result diagram of the myocardial tissue of the model group rats (×40).

[0047] Figure 23 It is the Masson staining result diagram of the myocardial tissue of the low-dose group rats (×40).

[0048] Figure 24 It is the Masson staining result diagram of the myocardial tissue of the medium-dose group rats (×40).

[0049] Figure 25 It is the Masson staining result diagram of the myocardial tissue of the high-dose group rats (×40).

[0050] Figure 26 It is the Masson staining result diagram of the myocardial tissue of the positive drug group rats (×40).

[0051] Figure 27 It is the detection result diagram of the TC content of each group of rats.

[0052] Figure 28 It is the detection result diagram of the TG content of each group of rats.

[0053] Figure 29 It is the detection result diagram of the LDL-C content of each group of rats.

[0054] Figure 30 It is the detection result diagram of the HDL-C content of each group of rats.

[0055] Figure 31 It is the detection result diagram of the IL-1β content of each group of rats.

[0056] Figure 32 It is the detection result graph of the IL-6 content of each group of rats.

[0057] Figure 33 It is the detection result graph of the TNF-α content of each group of rats.

[0058] Figure 34 It is the detection result graph of the MPO content of each group of rats.

[0059] Figure 35 It is the detection result graph of the Resistin content of each group of rats.

[0060] Figure 36 It is the detection result graph of the iNOS content of each group of rats.

[0061] Figure 37 It is the detection result graph of the MMP-8 content of each group of rats.

[0062] Figure 38 It is the detection result graph of the MMP-9 content of each group of rats.

[0063] Figure 39 It is the detection result graph of the ACE content of each group of rats.

[0064] Figure 40 It is the detection result graph of the IL-6 mRNA of each group of rats.

[0065] Figure 41 It is the detection result graph of the TNF-α mRNA of each group of rats.

[0066] Figure 42 It is the detection result graph of the MCP-1 mRNA of each group of rats.

[0067] Figure 43 It is the detection result graph of the LP-PLA2 mRNA of each group of rats.

[0068] Figure 44 It is the change graph of the inflammatory protein expression level in the myocardial tissue of each group of rats.

[0069] Figure 45 It is the detection result graph of NOD-2 of each group of rats.

[0070] Figure 46 It is the detection result graph of IL-1β of each group of rats.

[0071] Figure 47 It is the detection result graph of E-selectin of each group of rats.

[0072] Figure 48 It is the detection result graph of LOX-1 of each group of rats.

[0073] Figure 49 These are the detection result graphs of CHI3L-1 in each group of rats.

[0074] Figure 50 These are the detection result graphs of TIMP-3 in each group of rats.

[0075] Figure 51 These are the detection result graphs of ACE-2 in each group of rats.

[0076] Figure 52 These are the detection result graphs of GDF-15 in each group of rats.

[0077] Figure 53 These are the changes in the expression levels of pathway proteins in the myocardial tissues of each group of rats.

[0078] Figure 54 These are the detection result graphs of TLR4 in each group of rats.

[0079] Figure 55 These are the detection result graphs of cytoplasmic NF-κB P65 in each group of rats.

[0080] Figure 56 These are the detection result graphs of nuclear NF-κB P65 in each group of rats. Detailed implementation manners

[0081] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention will be described in detail below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other implementation manners obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope protected by the present invention.

[0082] Example 1

[0083] This example provides a preparation method for Danshu Fuyuan Formula, specifically: 25 g of Salvia miltiorrhiza, 10 g of Atractylodes macrocephala, 25 g of Astragalus membranaceus, 10 g of Lonicera japonica, 10 g of Polygonum cuspidatum, 10 g of Curcuma aromatica, 10 g of Poria cocos, 25 g of Coix lacryma-jobi and 10 g of Notopterygium incisum are pulverized and then mixed to obtain a composition, and then it is conventionally processed into tablets.

[0084] Example 2

[0085] This example provides a preparation method for Danshu Fuyuan Formula, specifically: 35 g of Salvia miltiorrhiza, 15 g of Atractylodes macrocephala, 35 g of Astragalus membranaceus, 20 g of Lonicera japonica, 20 g of Polygonum cuspidatum, 20 g of Curcuma aromatica, 15 g of Poria cocos, 35 g of Coix lacryma-jobi and 15 g of Notopterygium incisum are mixed and then pulverized to obtain a composition, and then it is conventionally processed into capsules.

[0086] Example 3

[0087] This embodiment provides a preparation method of Danshu Fuyuan Formula, specifically: Mix 30 g of Salvia miltiorrhiza, 12 g of Atractylodes macrocephala, 30 g of Astragalus membranaceus, 15 g of Lonicera japonica, 15 g of Polygonum cuspidatum, 15 g of Curcuma aromatica, 12 g of Poria cocos, 30 g of Coix lacryma-jobi, and 12 g of Notopterygium incisum, and perform extraction and refinement according to conventional processes to obtain granules.

[0088] Example 4

[0089] The difference between Example 4 and Example 3 is that the Danshu Fuyuan Formula is made into pills.

[0090] Example 5

[0091] The difference between Example 5 and Example 3 is that the Danshu Fuyuan Formula is made into powder.

[0092] Example 6

[0093] The difference between Example 6 and Example 3 is that the Danshu Fuyuan Formula is made into oral liquid.

[0094] Verification Example

[0095] (I) Experimental Method

[0096] 85 SPF male Wistar rats, weighing 180 ± 20 g, were randomly divided into a sham operation group, a model group, a low-dose Danshu Fuyuan Formula group (prepared in Example 3, hereinafter referred to as the low-dose group), a medium-dose Danshu Fuyuan Formula group (prepared in Example 3, hereinafter referred to as the medium-dose group), a high-dose Danshu Fuyuan Formula group (prepared in Example 3, hereinafter referred to as the high-dose group), and a positive drug group (the positive drug is Danwei Tablets). Among them, there were 10 rats in the sham operation group, and 15 rats in each of the other groups.

[0097] The sham operation group was fed with normal diet daily, and the remaining rats (75 rats) in each group were fed with high-fat diet daily for 8 consecutive weeks. Four weeks after feeding with high-fat diet, the left anterior descending coronary artery ligation was performed on the rats in the modeling group for modeling. On the second day after the operation, the rats in the positive drug group (left anterior descending coronary artery ligation + Danlou tablets) were given 0.47 g / Kg aqueous solution of Danlou tablets by gavage, and the rats in the low-dose group, medium-dose group, and high-dose group (left anterior descending coronary artery ligation + Danshu Fuyuan formula) were given 1.25 g / Kg, 2.5 g / Kg, and 5 g / Kg aqueous solution of Danshu Fuyuan formula by gavage respectively. The rats in the coronary heart disease model group (left anterior descending coronary artery ligation) and the sham operation group (only threading without ligation) were given an equal amount of distilled water by gavage once a day for 4 consecutive weeks. Four weeks after administration, blood was taken from the abdominal aorta of the rats to measure the levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and the levels of serum IL-6, TNF-α, IL-1β, MMP-9, MPO, Resistin, ACE, MMP-8, and iNOS were detected by enzyme-linked immunosorbent assay (ELISA). The heart tissues of the rats were taken, and HE staining and Masson staining were used to observe the myocardial cell and collagen hyperplasia conditions. The mRNA expression levels of myocardial IL-6, TNF-α, MCP-1, and LP-PLA2 were detected by PCR method, and the protein expressions of NOD-2, IL-1β, E-selection, LOX-1, CHI3L-1, TIMP-3, GDF-25, and ACE-2 in the myocardial tissues, as well as the protein levels of TLR4, cytoplasmic NF-κBp65, and nuclear NF-κBp65 were detected by Western Blot.

[0098] (II) Experimental Contents and Results

[0099] 1. Effects of Danshu Fuyuan formula on myocardial enzymes in rats with coronary heart disease:

[0100] After 4 weeks of intervention with Danshu Fuyuan formula, the levels of serum myocardial enzymes in rats with coronary heart disease were detected. The specific results are shown in Figure 1 、 Figure 2 . Compared with the sham operation group, the activities of serum CK-MB and LDH in the model group were significantly increased (▲▲▲▲P < 0.0001), showing statistical differences; compared with the model group, the activities of CK-MB and LDH in the low-dose group, medium-dose group, and high-dose group were significantly decreased (****P < 0.0001).

[0101] The results showed that Danshu Fuyuan formula could improve the levels of myocardial enzymes in rats with coronary heart disease.

[0102] 2. Effects of Danshu Fuyuan formula on cardiac function in rats with coronary heart disease:

[0103] After 4 weeks of intervention with Danshu Fuyuan Prescription, cardiac function was detected by echocardiography. The specific results are shown in Figures 3 to 12 . Compared with the sham operation group, the EF and FS of the rats in the model group were significantly decreased (▲▲▲▲P<0.0001), and the IVSd and IVSs were significantly thinned (▲▲P<0.01 or ▲▲▲▲P<0.0001), showing statistical differences. Compared with the model group, the low-dose group, medium-dose group, and high-dose group could all significantly increase the levels of EF, FS, IVSd, and IVSs (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001), and showed a dose-dependent manner.

[0104] The results showed that Danshu Fuyuan Prescription could improve the cardiac function of coronary heart disease rats.

[0105] 3. Effects of Danshu Fuyuan Prescription on myocardial ischemia in coronary heart disease rats:

[0106] As Figure 13 shown, the normal myocardial tissue of rats showed dark red, while the infarcted myocardial tissue showed pale white. The infarct area was measured using Image J software. As Figure 14 the results in showed, compared with the sham operation group, the myocardial infarct area of the rats in the model group was significantly increased (▲▲▲▲P<0.0001), showing statistical differences, indicating that the model was successfully established. Compared with the model group, the myocardial infarct area of the rats in the low-dose group, medium-dose group, and high-dose group was significantly decreased (***P<0.001).

[0107] The results showed that Danshu Fuyuan Prescription could improve the myocardial ischemia state of coronary heart disease rats.

[0108] 4. Effects of Danshu Fuyuan Prescription on the myocardial pathological state of coronary heart disease rats:

[0109] As Figures 15 to 20 shown, the HE staining results showed that the overall structure of the myocardial tissue of the rats in the sham operation group was intact, the myocardial cells were of normal size, arranged neatly and densely, and almost no inflammatory cell infiltration was seen, and there was no atrophy or apoptosis of muscle fibers. Compared with the sham operation group, the myocardial cells of the rats in the model group were arranged disorderly and loosely, the tissue was discontinuous, there was inflammatory cell infiltration between cells, and obvious interstitial edema was seen. Compared with the model, after treatment with the low-dose group, medium-dose group, and high-dose group, the above situations were alleviated to varying degrees, the myocardial tissue was arranged basically regularly and densely, and there was a small amount of inflammatory cell infiltration.

[0110] Masson staining was used to analyze the degree of myocardial fibrosis in each group of rats. As Figures 21 to 26As shown, the blue-stained area is the positive area of fibrosis. In the myocardial tissue of the sham operation group rats, cardiomyocytes were arranged neatly, myocardial fibers were arranged regularly, and a small amount of stained fibrous tissue was visible in focal areas, with only a small amount of collagen fiber hyperplasia. In the model group rats, a large number of cardiomyocytes were necrotic, the remaining cardiomyocytes were arranged disorderly, cardiomyocytes were sparse, and myocardial fibrosis was obvious. In the low-dose group, medium-dose group, and high-dose group rats, the degree of myocardial fibrosis was significantly reduced, the fibrotic area was significantly decreased, and the drug effect was remarkable.

[0111] The results showed that Danshu Fuyuan Recipe could improve the pathological state of coronary heart disease rats.

[0112] 5. Effects of Danshu Fuyuan Recipe on blood lipids in coronary heart disease rats:

[0113] Compared with the sham operation group, the contents of serum TC, TG, and LDL-C in the model group rats were all significantly increased (▲▲▲P < 0.001 or ▲▲▲▲P < 0.0001), and the level of HDL-C was significantly decreased (▲▲▲P < 0.001). Compared with the model group, the TC levels in the medium-dose group, high-dose group, and positive drug group were significantly decreased (*P < 0.05, ****P < 0.0001), the TG and LDL-C levels in the high-dose group and positive drug group were both significantly decreased (**P < 0.01), while the HDL-C level was significantly increased (*P < 0.05). The specific results are shown in Figures 27 to 30 。

[0114] The results showed that Danshu Fuyuan Recipe could improve the blood lipid levels of coronary heart disease rats.

[0115] 6. Effects of Danshu Fuyuan Recipe on serum inflammatory factors in coronary heart disease rats:

[0116] The effects of Danshu Fuyuan Recipe on the levels of serum IL-1β, IL-6, TNF-α, MPO, Resistin, iNOS, MMP-8, MMP-9, and ACE in coronary heart disease rats are shown in Figures 31 to 39 。Compared with the sham operation group, the levels of IL-1β, IL-6, TNF-α, MPO, Resistin, iNOS, MMP-8, MMP-9, and ACE in the model group rats were all significantly increased (▲▲▲▲P < 0.0001); compared with the model group rats, the levels of IL-1β, IL-6, TNF-α, Resistin, MMP-9, and ACE in the low-dose group, medium-dose group, and high-dose group rats were all significantly decreased (*P < 0.05, **P < 0.01, ***P < 0.001 or ****P < 0.0001). The MMP-8 levels in the medium-dose group and high-dose group rats were significantly decreased (***P < 0.001, ****P < 0.0001). Only the serum MPO and iNOS in the high-dose group rats were significantly decreased (****P < 0.0001).

[0117] Results showed that Danshu Fuyuan Prescription could improve the serum inflammation level in rats with coronary heart disease.

[0118] 7. Changes in the mRNA levels of inflammatory factors in the myocardial tissue of rats with coronary heart disease treated with Danshu Fuyuan Prescription:

[0119] Compared with the sham operation group, the mRNA transcription levels of IL-6, TNF-α, MCP-1, and LP-PLA2 in the myocardial tissue of rats in the model group were significantly increased (▲▲▲▲P < 0.0001); compared with the model group, the mRNA transcription levels of IL-6, TNF-α, MCP-1, and LP-PLA2 in the myocardial tissue of rats in the low-dose group, medium-dose group, and high-dose group were all decreased (****P < 0.0001). The results are shown in Figures 40 to 43 .

[0120] Results showed that Danshu Fuyuan Prescription could improve the mRNA transcription in the myocardial tissue of rats with coronary heart disease.

[0121] 8. Effects of Danshu Fuyuan Prescription on the expression of inflammatory proteins in the myocardial tissue of rats with coronary heart disease:

[0122] The effects of Danshu Fuyuan Prescription on the protein expression of NOD-2, IL-1β, E-selectin, LOX-1, CHI3L-1, TIMP-3, ACE-2, and GDF-15 in the myocardium of rats with coronary heart disease are shown in Figures 44 to 52 . Compared with the sham operation group, the protein levels of NOD-2, IL-1β, E-selectin, LOX-1, CHI3L-1, and GDF-15 in the myocardial tissue of rats in the model group were significantly increased (▲▲▲▲P < 0.0001), and the expressions of TIMP-3 and ACE-2 were significantly decreased (▲▲▲▲P < 0.0001); compared with the model group, the levels of E-selectin, CHI3L-1, and GDF-15 in the myocardial tissue of rats in the low-dose group, medium-dose group, and high-dose group were significantly decreased (**P < 0.01 or ****P < 0.0001). In the medium-dose group and high-dose group, the expressions of NOD-2, IL-1β, and LOX-1 in the myocardial tissue of rats were significantly decreased, and the expressions of TIMP-3 and ACE-2 were significantly increased (**P < 0.01 or ****P < 0.0001).

[0123] Results showed that Danshu Fuyuan Prescription could improve the expression of inflammatory proteins in the myocardial tissue of rats with coronary heart disease.

[0124] 9. Effects of Danshu Fuyuan Prescription on the expression of pathway proteins in the myocardial tissue of rats with coronary heart disease:

[0125] Compared with the sham operation group, the expressions of TLR4 and nuclear NF-κB P65 in the myocardial tissues of rats in the model group were significantly increased (▲▲▲▲P<0.0001), and the cytoplasmic NF-κB P65 was significantly decreased; compared with the model group, the expressions of TLR4 in the myocardial tissues of rats in the medium-dose group and high-dose group were significantly decreased (****P<0.0001), the cytoplasmic NF-κB P65 was significantly increased (****P<0.0001), and the nuclear NF-κB P65 in the myocardial tissues of rats in the high-dose group was significantly decreased (****P<0.0001). The specific results are shown in Figures 53 to 56 .

[0126] The results showed that Danshu Fuyuan Formula could improve the expression of pathway proteins in the myocardial tissues of rats with coronary heart disease.

[0127] As described above, it is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. Use of a Danshu Fuyuan Formula in the preparation of a drug for treating coronary heart disease, characterized in that, The raw materials of the Danshu Fuyuan Prescription are in a weight ratio of: 25-35 parts of Salvia miltiorrhiza, 10-15 parts of Atractylodes macrocephala, 25-35 parts of Astragalus membranaceus, 10-20 parts of Lonicera japonica, 10-20 parts of Polygonum cuspidatum, 10-20 parts of Curcuma aromatica, 10-15 parts of Poria cocos, 25-35 parts of Coix lacryma-jobi, and 10-15 parts of Notopterygium incisum.

2. The use according to claim 1, characterized in that, The raw materials of the Danshu Fuyuan Prescription are in a weight ratio of: 30 parts of Salvia miltiorrhiza, 12 parts of Atractylodes macrocephala, 30 parts of Astragalus membranaceus, 15 parts of Lonicera japonica, 15 parts of Polygonum cuspidatum, 15 parts of Curcuma aromatica, 12 parts of Poria cocos, 30 parts of Coix lacryma-jobi, and 12 parts of Notopterygium incisum.

3. The use according to claim 1 or 2, characterized in that, The preparation method of the Danshu Fuyuan Prescription is as follows: Crush the raw materials of the Danshu Fuyuan Prescription and then mix them to obtain a composition; Or, mix the raw materials of the Danshu Fuyuan Prescription and then crush them to obtain a composition; Or, extract and refine the raw materials of the Danshu Fuyuan Prescription according to the conventional process to obtain one of tablets, capsules, granules, pills, powders or oral liquids.

4. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the myocardial enzyme level of coronary heart disease.

5. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the cardiac function of coronary heart disease.

6. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the myocardial ischemia state of coronary heart disease.

7. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the pathological state of coronary heart disease.

8. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the blood lipid level of coronary heart disease.

9. The use according to claim 1 or 2, characterized in that, The drug is a drug for improving the serum inflammation level of coronary heart disease; and / or, the drug is a drug for improving the mRNA transcription of myocardial tissue in coronary heart disease; and / or, the drug is a drug for improving the expression of inflammatory proteins in myocardial tissue of coronary heart disease; and / or, the drug is a drug for improving the expression of pathway proteins in myocardial tissue of coronary heart disease.

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