CN115487260B

CN115487260B - Traditional Chinese medicine composition for treating hypercholesterolemia or atherosclerosis and application thereof

Info

Publication number: CN115487260B
Application number: CN202211336548.4A
Authority: CN
Inventors: 王肖龙; 李益萍; 王慧颖; 张春伶
Original assignee: Shuguang Hospital Affiliated to Shanghai University of TCM
Current assignee: Shuguang Hospital Affiliated to Shanghai University of TCM
Priority date: 2022-10-28
Filing date: 2022-10-28
Publication date: 2023-06-20
Anticipated expiration: 2042-10-28
Also published as: CN115487260A

Abstract

The invention provides a traditional Chinese medicine composition for treating hypercholesterolemia or atherosclerosis, which is prepared from the following raw materials in parts by weight: 20-40 parts of astragalus membranaceus, 2-10 parts of ginseng, 9-21 parts of Chinese yam, 9-21 parts of prepared rehmannia root, 9-21 parts of poria cocos, 3-15 parts of purified pinellia tuber, 6-18 parts of dried orange peel, 6-18 parts of red sage root, 9-21 parts of Chinese angelica, 10-30 parts of rhizoma alismatis and 2-10 parts of coptis chinensis. The invention also provides application of the traditional Chinese medicine composition. The advantages are that: the traditional Chinese medicine composition can effectively reduce endogenous cholesterol synthesis and promote liver cholesterol excretion, so that LDL-C level in serum is reduced, liver lipid deposition is improved, and the anti-atherosclerosis effect is exerted.

Description

Traditional Chinese medicine composition for treating hypercholesterolemia or atherosclerosis and application thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating hypercholesterolemia or atherosclerosis and application thereof.

Background

Cardiovascular disease is one of the major "murders" that jeopardizes the health of all humans. In recent years, cardiovascular diseases have seen an increasing trend towards younger age, mainly in the form of atherosclerosis. Atherosclerosis (AS) is the major pathological basis of cardiovascular disease. Lipid metabolism disorders play a critical role in the development of cardiovascular disease, and interaction of hyperlipidemia with other risk factors may lead to the formation of atherosclerotic plaques and the development of other cardiovascular diseases, thus effectively controlling blood lipid levels, inhibiting atherosclerosis formation and reducing the risk of cardiovascular events.

The traditional Chinese medicine has wide application prospect in treating atherosclerosis, and can provide a new idea for preventing and treating atherosclerosis by carrying out deep research on the action mechanism of a traditional Chinese medicine compound with definite curative effect in clinical practice. The traditional Chinese medicine considers that the disease position of atherosclerosis is mainly in blood vessels, which is related to eating disorder, senile body weakness, seven emotions internal injury and deficiency of the body due to the above factors, so that phlegm turbidity and blood stasis are blocked in the veins, and limb bones and internal organs are malformed due to malnutrition. The research and development of the medicine for resisting hyperlipidemia and atherosclerosis has wide market prospect and social significance.

Chinese patent document CN:202211015547.X discloses a pharmaceutical composition for the treatment of atherosclerosis and its preparation method. The composite material consists of the following components in parts by weight: 5 to 15 parts of fructus amomi, 2 to 8 parts of sea buckthorn, 2 to 8 parts of dried ginger, 2 to 8 parts of combined spicebush root, 2 to 8 parts of American ginseng, 2 to 8 parts of fructus cnidii and 1 to 3 parts of nutgrass galingale rhizome, and the obtained composition has remarkable effect of treating atherosclerosis.

Disclosure of Invention

The invention aims at overcoming the defects in the prior art and provides a traditional Chinese medicine composition for treating hypercholesterolemia or atherosclerosis.

The invention also aims at providing the application of the traditional Chinese medicine composition.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

a traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases is prepared from the following raw materials in parts by weight: 20-40 parts of astragalus membranaceus, 2-10 parts of ginseng, 9-21 parts of Chinese yam, 9-21 parts of prepared rehmannia root, 9-21 parts of poria cocos, 3-15 parts of purified pinellia tuber, 6-18 parts of dried orange peel, 6-18 parts of red sage root, 9-21 parts of Chinese angelica, 10-30 parts of rhizoma alismatis and 2-10 parts of coptis chinensis.

Preferably, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 25-35 parts of astragalus membranaceus, 4-8 parts of ginseng, 12-18 parts of Chinese yam, 12-18 parts of prepared rehmannia root, 12-18 parts of poria cocos, 6-12 parts of purified pinellia tuber, 9-15 parts of dried orange peel, 9-15 parts of red sage root, 12-18 parts of Chinese angelica, 15-25 parts of rhizoma alismatis and 4-8 parts of coptis chinensis.

More preferably, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 parts of astragalus, 6 parts of ginseng, 15 parts of Chinese yam, 15 parts of prepared rehmannia root, 15 parts of poria cocos, 9 parts of purified pinellia tuber, 12 parts of dried orange peel, 12 parts of red sage root, 15 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 6 parts of coptis root.

Preferably, the traditional Chinese medicine composition is in the form of granules, tablets, capsules, oral liquid, mixture or syrup.

In order to achieve the second purpose, the invention adopts the following technical scheme:

the application of the traditional Chinese medicine composition in preparing medicines for treating cardiovascular diseases.

Preferably, the cardiovascular and cerebrovascular diseases are hypercholesterolemia and/or atherosclerosis.

The invention has the advantages that:

1. ginseng and astragalus root are monarch drugs for strengthening spleen and tonifying qi, helping spleen and transforming; the Chinese yam and the prepared rehmannia root can tonify the kidney and qi, tonify the congenital and acquired, and assist the ginseng and the astragalus root to invigorate the spleen so as to assist transportation and transformation, and are ministerial drugs; the pinellia tuber and the dried orange peel dry dampness and resolve phlegm, the poria cocos and the rhizoma alismatis promote diuresis and remove dampness, so that damp evil is removed from lower jiao, the sources of phlegm and chemical transformation are reduced, and the red sage root and the Chinese angelica are used as adjuvant drugs for activating blood and dissolving stasis; coptis chinensis, rhizoma Coptidis, which is a guiding drug for preventing yin injury due to warm herbs. The medicines are synergistic to supplement each other and play roles in strengthening body resistance and eliminating pathogenic factors, tonifying qi and nourishing blood, and activating blood circulation to dissipate blood stasis.

2. The traditional Chinese medicine composition has remarkable treatment effect on atherosclerosis and is stronger than a western medicine rosuvastatin calcium tablet.

Drawings

Figure 1 is a graph of body mass after treatment for each group of mice (note: compared to model group, ^# P<0.05， ^## P<0.01)；

FIG. 2 is a comparison (X40) of aortic sinus atherosclerotic lesions (note: comparison to blank group, P) of mice of each group<0.05; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05)；

FIG. 3 is a comparison of the accumulation of Dou Zhi mass in the aorta (X40) of mice in each group;

FIG. 4 is a comparison of the fiber content of the aorta Dou Jiaoyuan of each group of mice (X40);

FIG. 5 is a liver pathology comparison (X100) for each group of mice;

FIG. 6 is a graph showing blood lipid index comparison (note: to blank group ratio, P)<0.01; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01)；

FIG. 7 is the effect of the spleen-invigorating and lipid-lowering formulation on mRNA associated with cholesterol absorption in the intestinal tract (note: as compared to model group, ^## P<0.01; compared with the western medicine group, the medicine is prepared, ^& P<0.05)；

FIG. 8 shows that the recipe for strengthening spleen and reducing blood lipid has an effect on mRN related to cholesterol synthesis in liverThe effect of a (note: to model set ratio, ^# P<0.05)；

FIG. 9 is a graph showing the effect of the spleen-invigorating and lipid-lowering formulation on cholesterol synthesis-related proteins in the liver (note: to blank ratio, P)<0.05, compared with the model group, ^# P<0.05)

FIG. 10 is the effect of the spleen-invigorating lipid-lowering formulation on mRNA associated with cholesterol transport in the liver (note: compared to model set, ^# P<0.05; compared with the western medicine group, the medicine is prepared, ^& P<0.05)；

FIG. 11 is a graph showing the effect of a spleen-invigorating lipid-lowering formulation on cholesterol transport-related proteins in the liver (note: compared to model set, ^# P<0.05; compared with the western medicine group, the medicine is prepared, ^& P<0.05)；

FIG. 12 is the effect of spleen-invigorating and lipid-lowering formulations on mRNA associated with reverse cholesterol transport in the liver (note: as compared to model set, ^# P<0.05， ^## P<0.01; compared with the western medicine group, the medicine is prepared, ^& P<0.05)；

FIG. 13 effect of spleen invigorating and lipid lowering formulation on cholesterol-related protein in liver (note: compared to model group, ^## P<0.01)；

FIG. 14 is the effect of the spleen-invigorating and lipid-lowering formulation on mRNA associated with cholesterol excretion in the liver (note: compared to model group, ^# P<0.05， ^## P<0.01)；

FIG. 15 is a graph showing the effect of the spleen-invigorating and lipid-lowering formulation on cholesterol excretion-related proteins in the liver (note: to blank ratio, P<0.05; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01)；

FIG. 16 is a graph showing the effect of the spleen-invigorating and lipid-lowering formulation on cholesterol nuclear transcription factor and nuclear receptor-associated mRNA in the liver (note: vs. blank,..times.P)<0.05; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05)；

Detailed Description

The invention is further described below in conjunction with the detailed description. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. Further, it is understood that various changes and modifications of the present invention may be made by those skilled in the art after reading the description of the present invention, and such equivalents are intended to fall within the scope of the claims appended hereto.

Example 1A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis

30 parts of astragalus, 6 parts of ginseng, 15 parts of Chinese yam, 15 parts of prepared rehmannia root, 15 parts of poria cocos, 9 parts of purified pinellia tuber, 12 parts of dried orange peel, 12 parts of red sage root, 15 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 6 parts of coptis chinensis, and decocting by a conventional method.

Example 2A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (II)

30 parts of astragalus, 4 parts of ginseng, 18 parts of Chinese yam, 9 parts of prepared rehmannia root, 21 parts of poria cocos, 9 parts of purified pinellia tuber, 9 parts of dried orange peel, 15 parts of red sage root, 9 parts of Chinese angelica, 30 parts of oriental waterplantain rhizome and 6 parts of coptis chinensis, and decocting by a conventional method.

Example 3A Chinese medicinal composition (III) for treating hypercholesterolemia or atherosclerosis

25 parts of astragalus, 8 parts of ginseng, 9 parts of Chinese yam, 21 parts of prepared rehmannia root, 15 parts of poria cocos, 6 parts of purified pinellia tuber, 15 parts of dried orange peel, 6 parts of red sage root, 21 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 4 parts of coptis chinensis, and decocting by a conventional method.

Example 4A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (IV)

35 parts of astragalus, 2 parts of ginseng, 21 parts of Chinese yam, 15 parts of prepared rehmannia root, 12 parts of poria cocos, 12 parts of purified pinellia tuber, 6 parts of dried orange peel, 18 parts of red sage root, 15 parts of Chinese angelica, 15 parts of oriental waterplantain rhizome and 8 parts of coptis chinensis, and decocting by a conventional method.

Example 5A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (V)

20 parts of astragalus, 10 parts of ginseng, 15 parts of Chinese yam, 12 parts of prepared rehmannia root, 18 parts of poria cocos, 3 parts of purified pinellia tuber, 18 parts of dried orange peel, 12 parts of red sage root, 12 parts of Chinese angelica, 25 parts of oriental waterplantain rhizome and 2 parts of coptis chinensis, and decocting by a conventional method.

Example 6A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (six)

40 parts of astragalus, 6 parts of ginseng, 12 parts of Chinese yam, 18 parts of prepared rehmannia root, 9 parts of poria cocos, 15 parts of purified pinellia tuber, 12 parts of dried orange peel, 9 parts of red sage root, 18 parts of Chinese angelica, 10 parts of oriental waterplantain rhizome and 10 parts of coptis chinensis, and decocting by a conventional method.

Example 7A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (seventh)

30 parts of astragalus, 8 parts of ginseng, 9 parts of Chinese yam, 21 parts of prepared rehmannia root, 15 parts of poria cocos, 6 parts of purified pinellia tuber, 15 parts of dried orange peel, 6 parts of red sage root, 21 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 4 parts of coptis chinensis, and decocting by a conventional method.

Example 8A Chinese medicinal composition (eight) for treating hypercholesterolemia or atherosclerosis

25 parts of astragalus, 2 parts of ginseng, 21 parts of Chinese yam, 15 parts of prepared rehmannia root, 12 parts of poria cocos, 12 parts of purified pinellia tuber, 6 parts of dried orange peel, 18 parts of red sage root, 15 parts of Chinese angelica, 15 parts of oriental waterplantain rhizome and 8 parts of coptis chinensis, and decocting by a conventional method.

Example 9A Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis (nine)

35 parts of astragalus, 10 parts of ginseng, 15 parts of Chinese yam, 12 parts of prepared rehmannia root, 12 parts of poria cocos, 6 parts of purified pinellia tuber, 18 parts of dried orange peel, 12 parts of red sage root, 12 parts of Chinese angelica, 25 parts of oriental waterplantain rhizome and 2 parts of coptis chinensis, and decocting by a conventional method.

Example 10A Chinese medicinal composition (ten) for treating hypercholesterolemia or atherosclerosis

20 parts of astragalus, 6 parts of ginseng, 12 parts of Chinese yam, 18 parts of prepared rehmannia root, 9 parts of poria cocos, 15 parts of purified pinellia tuber, 12 parts of dried orange peel, 9 parts of red sage root, 18 parts of Chinese angelica, 10 parts of oriental waterplantain rhizome and 10 parts of coptis chinensis, and decocting by a conventional method.

Example 11A Chinese medicinal composition for the treatment of hypercholesterolemia or atherosclerosis (eleven)

40 parts of astragalus, 4 parts of ginseng, 18 parts of Chinese yam, 9 parts of prepared rehmannia root, 21 parts of poria cocos, 9 parts of purified pinellia tuber, 9 parts of dried orange peel, 15 parts of red sage root, 9 parts of Chinese angelica, 30 parts of oriental waterplantain rhizome and 6 parts of coptis chinensis, and decocting by a conventional method.

The conventional method of examples 1 to 11 is a conventional method for preparing a decoction of traditional Chinese medicine, wherein the decoction is prepared by soaking the medicinal materials for 1h, boiling with strong fire, boiling with slow fire for about 30min, filtering, repeating the decoction for 3 times, mixing the filtrates, and mixing to obtain decoction.

Example 12 preparation of a tablet/Capsule of Chinese medicinal composition for treating hypercholesterolemia or atherosclerosis

Taking the traditional Chinese medicine composition in any one of embodiments 1-11, adding 9-11 times of water, decocting for 2-3.5 hours, and filtering out the decoction. Adding 9 times of water, decocting for 2.5 hr, filtering to obtain decoction, mixing the two decoctions, standing, filtering to obtain supernatant, concentrating, cooling, adding 3 times of ethanol, and stirring to precipitate overnight. Collecting supernatant, concentrating to obtain soft extract; adding pharmaceutical adjuvants, vacuum drying, pulverizing, granulating, and making into tablet or capsule.

Example 13 preparation of a Chinese medicinal composition granule for treating hypercholesterolemia or atherosclerosis

Taking the traditional Chinese medicine composition in any one of embodiments 1-11, adding 8-10 times of water, decocting for 3 hours, and filtering out the decoction. Adding 10 times of water, decocting for 2.5 hr, filtering to obtain decoction, mixing the two decoctions, standing, filtering to obtain supernatant, concentrating, cooling, adding 2 times of ethanol, and stirring to precipitate overnight. Collecting supernatant, concentrating to obtain soft extract; adding proper pharmaceutical adjuvants, granulating, drying, grading to obtain 20g granule, and packaging into 10 g/bag.

Example 14 preparation of a Chinese medicinal composition mixture/oral liquid/syrup for treating hypercholesterolemia or atherosclerosis

Taking the traditional Chinese medicine composition in any one of embodiments 1-11, adding 8-11 times of water, decocting for 3 hours, and filtering out the decoction. Adding 8 times of water, decocting for 3 hr, filtering to obtain decoction, mixing the two decoctions, standing, filtering to obtain supernatant, concentrating, cooling, adding 3.5 times of ethanol, and stirring to precipitate overnight. Collecting supernatant, concentrating to obtain soft extract; adding proper pharmaceutical adjuvants, and making into mixture, oral liquid or syrup.

Example 15 animal experiment

By establishing an Atherosclerosis (AS) mouse model, the formation mechanism of an atherosclerosis plaque is simulated, and the apoE gene knockout (ApoE) of the spleen strengthening and lipid lowering formula is observed ^-/- ) Effects of atherosclerotic plaque formation in mice. By detecting the serum blood lipid level and the liver lipid deposition level of mice, whether the spleen-strengthening lipid-lowering prescription plays a role in resisting atherosclerosis plaques by regulating lipid metabolism of mice or not is primarily discussedThe role of block formation. ApoE is prepared by researching spleen-strengthening lipid-lowering prescription ^-/- The regulation and mechanism of spleen-strengthening and lipid-lowering formulation on cholesterol homeostasis are discussed in terms of the effects of nuclear transcription factors, nuclear receptors in the liver of mice, cholesterol absorption in the intestinal tract, and the expression of mRNA and protein levels in the liver, such as cholesterol synthesis, transport, reverse transport, excretion, etc.

1 materials and methods

1.1 materials

1.1.1 animals

SPF grade ApoE 8 weeks old ^-/- Male mice, 24, purchased from Beijing vitamin Torilhua Corp., eligibility number: SCXK 2016-0011, raised by the university of Shanghai Chinese medicine laboratory animal center, drunk and ingested freely.

1.1.2 medicaments

Spleen-invigorating and lipid-lowering formula: 30 parts of astragalus, 6 parts of ginseng, 15 parts of Chinese yam, 15 parts of prepared rehmannia root, 15 parts of poria cocos, 9 parts of purified pinellia tuber, 12 parts of dried orange peel, 12 parts of red sage root, 15 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 6 parts of coptis chinensis (purchased from Shanghai traditional Chinese medicine university affiliated dawn hospital).

Western medicine group: rosuvastatin calcium tablet (10 mg (African pharmaceutical Co., ltd., lot number: 132756).

High fat diet feed (78.8% of breeding mouse feed, 10% of lard, 10% of yolk powder, 1% of cholesterol and 0.2% of bile salt, purchased from Jiangsu province collaborative medical bioengineering company, and produced license number is Su Sizheng (2014) 01008).

1.2 method

1.2.1 grouping

8 week old male ApoE ^-/- Mice were fed adaptively for 1 week, randomly divided into model group, western medicine group, spleen-invigorating and lipid-lowering prescription group, 6 mice per group, and fed with high-fat feed. 6 mice were also fed as basal diet to the blank group.

1.2.2 administration

(1) Blank group: the mice were fed with normal mouse feed and were given equal amounts of distilled water daily for gastric lavage.

(2) Model group: the western high fat feed was used for feeding, and an equal amount of distilled water was administered daily to perfuse the stomach.

(3) Western medicine group: based on western high-fat feed, the medicine is administrated by stomach irrigation according to the mass of 2.08mg/kg of the crude drug containing the settable drug every day.

(4) The traditional Chinese medicine group: based on western high-fat feed, the feed is fed by lavage according to the body mass of 32.24g/kg of the crude drug containing the spleen-strengthening lipid-lowering prescription every day, and the feed is continuously fed for 12 weeks to obtain the materials.

The body mass of each group of mice was weighed from 1 pm on the first day of the experiment, then once a week at the same time, and the body mass was weighed before drawing materials.

1.2.3 statistical methods

Data analysis was performed using SPSS 20.0 statistical software, experimental data to

The differences between the average values of the groups were examined by single-factor analysis of variance, and the LSD method or Dunnett T3 method was used for the pairwise comparison. The difference of P <0.05 is statistically significant.

2. Results

2.1 comparison of the quality of mice in each group

The body mass level between groups of mice before treatment was not statistically significant. After 12 weeks, the western group mice showed a significant decrease in constitution level compared to the model group, and the difference was statistically significant (P < 0.01). Compared with the model group, the mice in the spleen-invigorating and lipid-lowering prescription group have reduced body quality level, and the difference has statistical significance (P < 0.05) (table 1, figure 1).

Table 1 comparison of the quality of mice in each group

Note that: compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01

2.2 Effect of spleen-invigorating and lipid-lowering formulation on plaque formation at the aortic sinus of mice

Microscopic observation shows that no obvious atherosclerosis plaque is formed at the aortic sinus of the mice in the blank group, more obvious atherosclerosis plaque is formed at the aortic sinus of the mice in the model group, and the area of the atherosclerosis plaque formed at the aortic sinus of the mice in the spleen-strengthening lipid-lowering square group is smaller. The statistical result shows that compared with a blank group, the lesion area at the aortic sinus of the model group is increased, and the difference has statistical significance (P < 0.05); compared with the model group, the western medicine group and the spleen-strengthening and lipid-lowering prescription group have reduced lesion areas at aortic sinuses, and the difference has statistical significance (P < 0.05) (table 2, figure 2).

Table 2 comparison of aortic sinus plaque formation in groups of mice under HE staining

Note that: compared with the blank group, ^* P<0.05; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05。

2.3 Effect of spleen-invigorating and lipid-lowering formulation on lipid accumulation at the aortic sinus of mice

Oil red O was able to bind specifically to lipid deposition at the aortic sinus of mice in red (as shown in grey in the description), so that the rat aortic sinus was observed by staining sections of aorta Dou Bingdong with oil red O in this study. The microscopic observation results show that only a small amount of lipid deposition is visible at the aortic sinus of the mice in the blank group, and a large amount of lipid deposition is visible at the aortic sinus of the mice in the model group. Compared with the model group, the western medicine group and the spleen-strengthening lipid-lowering formula group have a reduced tendency of lipid deposition at the aortic sinus of the mice. (Table 3, FIG. 3)

TABLE 3 comparison of the accumulation of Dou Zhi mass in the aorta of groups of mice stained with oil red O

2.4 Effect of spleen-invigorating and lipid-lowering formulation on collagen fiber content at aortic sinus of mice

Changes in collagen fiber content in plaque of mice of each group can be shown after Masson staining, and after staining, the muscle fibers are red (grey in the specification, so that the color is described), the collagen fibers are blue (grey in the specification, so that the color is described), and the content of the collagen fibers is related to plaque stability. The results show that compared with the model group, the collagen fiber content in the plaque of the mice in the spleen-strengthening lipid-lowering prescription group tends to be increased, and the pathological results indicate that the spleen-strengthening lipid-lowering prescription group can increase the collagen fiber content in the plaque, thereby being beneficial to enhancing the stability of the plaque and reducing the risk of rupture of the atherosclerosis plaque while exerting the effect of preventing the formation of the atherosclerosis plaque. (Table 4, FIG. 4)

Table 4 comparison of fiber content of aortic Dou Jiaoyuan of groups of mice stained with Masson

2.5 liver pathology comparison of mice in groups

The liver tissue of the mice in the blank group is normal in appearance, smooth in coating and dark red in color (gray in the specification, so that the specification shows the liver tissue). The liver tissue volume of the mice in the model group is obviously increased, the color is yellow (gray in the specification, so that the mice in the model group are soft in texture and have greasy feel). The liver tissue structure of the mice in the blank group is clear, no obvious lipid deposition is seen, and no obvious fat drop is seen in liver cells; the liver tissue structure of the mice in the model group has obvious fuzzy lipid deposition, the fatty degeneration degree of liver cells is serious, and a plurality of fat drops with different areas appear in the cells. Compared with the model group, the western medicine group and the spleen-strengthening lipid-lowering formula group have different degrees of lessening of lipid deposition in liver tissues of mice. (FIG. 5)

2.6 comparison of blood lipid changes in mice of each group

The mice in the model group had significantly elevated serum TC, LDL-C levels compared to the blank group, and the differences were all statistically significant (P < 0.01). Compared with the model group, the serum LDL-C level of mice in western medicine group is significantly reduced (P < 0.01). Compared with the model group, the serum LDL-C level of mice in the spleen-strengthening and lipid-lowering prescription group is reduced, and the difference has statistical significance (P < 0.05). There was no statistical difference in TG, HDL-C between each group (Table 5, FIG. 6)

Table 5 comparison of blood lipid indicators for mice in each group

Note that: compared with the blank group, ^** P<0.01; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01。

2.7 Effect of spleen-invigorating and lipid-lowering formulation on cholesterol absorption-related mRNA in the intestinal tract

(1) NPC1L1: compared with the blank group, the mice in the model group have the ascending trend of the small intestine NPC1L 1mRNA level, but have no statistical significance. Compared with the model group, western medicine group mice have significantly increased levels of small intestine NPC1L 1mRNA, and the difference has statistical significance (P < 0.01). Compared with western medicine group, spleen-invigorating and lipid-lowering formula group mice have reduced levels of small intestine NPC1L 1mRNA, and the difference has statistical significance (P < 0.05).

(2) ABCG5: the mice in the model group had an ascending trend in small intestine ABCG5 mRNA levels compared to the blank group, but were not statistically significant. Compared with the model group, the spleen-strengthening lipid-lowering formula group mice have an ascending trend of the small intestine ABCG5 mRNA level, but have no statistical significance.

(3) ABCG8: the mice in the model group had an ascending trend in small intestine ABCG8 mRNA levels compared to the blank group, but were not statistically significant. Compared with the model group, the spleen-strengthening lipid-lowering formula group mice have the ascending trend of the small intestine ABCG8 mRNA level, but have no statistical significance.

(4) ACAT1: the mice in the model group had a reduced tendency to have small intestine ACAT1mRNA levels compared to the blank group. Compared with the model group, the western medicine group mice have significantly increased small intestine ACAT1mRNA levels, and the difference has statistical significance (P < 0.01). Compared with the model group, the spleen-strengthening lipid-lowering formula group mice have an ascending trend of small intestine ACAT1mRNA level.

(5) ACAT2: the mice in the model group had an ascending trend in small intestine ACAT 2mRNA levels compared to the blank group, but were not statistically significant. Compared with the model group, the spleen-invigorating and lipid-lowering formula group mice have significantly increased small intestine ACAT 2mRNA levels, and the difference has statistical significance (P < 0.01).

Compared with the blank group, the mice in the model group have the ascending trend of the level of the small intestine NPC1L1 and the ABCG5/8,ACAT1,ACAT2 mRNA. Compared with the model group, the spleen-strengthening lipid-lowering formula group mice have the advantages that the levels of the intestinal NPC1L1, the ABCG5/8 and the ACAT1 mRNAs are increased, and the levels of the ACAT2 mRNAs are obviously increased (P < 0.01). Compared with western medicine group, spleen-invigorating and lipid-lowering formula group mice have reduced levels of small intestine NPC1L 1mRNA (P < 0.05).

(Table 6, FIG. 7)

TABLE 6 influence of spleen-invigorating and lipid-lowering formulations on cholesterol absorption-related mRNAs in the intestinal tract

Note that: compared with the model group, the method has the advantages of high accuracy, ^## P<0.01; compared with the western medicine group, the medicine is prepared, ^& P<0.05。

2.8 effects of spleen-invigorating and lipid-lowering formulations on mRNA related to cholesterol synthesis in liver

Compared with the blank group, the liver HMGCR mRNA level of the mice in the model group has an ascending trend, and the difference has no statistical significance. Compared with the model group, the western medicine group and the spleen-strengthening lipid-lowering formula group have reduced liver HMGCR mRNA levels, and the difference has statistical significance (P < 0.05). (Table 7, FIG. 8)

TABLE 7 Effect of spleen invigorating and lipid lowering formulations on mRNA related to cholesterol synthesis in liver

Note that: compared with the model group, the method has the advantages of high accuracy, ^# P<0.05

2.9 Effect of spleen-invigorating and lipid-lowering formulation on cholesterol-synthesizing related proteins in liver

In order to investigate the effect of the spleen-strengthening lipid-lowering formulation in regulating and controlling the expression of HMGCR, quantitative analysis of HMGCR protein expression was performed according to the results of RT-PCR experiments. Experimental results showed that the liver HMGCR protein levels were reduced in the mice of the model group compared to the blank group, the differences being statistically significant (P < 0.05). Compared with the model group, the western medicine group has the advantages that the liver HMGCR protein level of the mice in the spleen-strengthening and lipid-lowering prescription group is reduced, and the differences have statistical significance (P is less than 0.05). (FIG. 9)

2.10 Effect of spleen invigorating and lipid lowering formulation on mRNA related to cholesterol transport in liver

(1) PCSK9: the liver PCSK9 mRNA levels tended to rise in the model group compared to the blank group. Compared with the model group, the liver PCSK9 mRNA level of the mice in the western medicine group is increased, and the difference has statistical significance (P < 0.05). Compared with western medicine, the liver PCSK9 mRNA level of the spleen-strengthening lipid-lowering mice is reduced, and the difference has statistical significance (P < 0.05)

(2) LDLR: compared with the blank group, the liver LDLR mRNA level of the mice in the model group has an ascending trend. Compared with the model group, the liver LDLR mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group has an ascending trend.

Compared with the blank group, the liver PCSK9 and LDLR mRNA levels of the mice in the model group have an ascending trend. Compared with the model group, the liver PCSK9 and LDLR levels of the mice in the spleen-strengthening and lipid-lowering prescription group are reduced, but the method has no statistical significance. (Table 8, FIG. 10)

TABLE 8 influence of spleen-invigorating and lipid-lowering formulations on cholesterol transport-related mRNAs in liver

Note that: compared with the model group, the method has the advantages of high accuracy, ^# P<0.05; compared with the western medicine group, the medicine is prepared, ^& P<0.05。

2.11 Effect of spleen invigorating and lipid lowering formulation on cholesterol transport related proteins in liver

To investigate the role of the spleen strengthening and lipid lowering formula in regulating and controlling LDLR expression, quantitative analysis is carried out on LDLR protein expression according to RT-PCR experimental results. The experimental results show that compared with the blank group, the liver LDLR protein level of the mice in the model group has an ascending trend. Compared with the model group, the liver LDLR protein level of the mice in the spleen-strengthening and lipid-lowering prescription group is increased, and the difference has statistical significance (P < 0.05). Compared with western medicine group, the liver LDLR protein level of mice in spleen-invigorating and lipid-lowering prescription group is increased, and the difference has statistical significance (P < 0.05). (FIG. 11)

2.12 effects of spleen invigorating and lipid lowering formulation on mRNA related to reverse cholesterol transport in liver

(1) LCAT: the liver LCAT mRNA levels tended to be reduced in the mice of the model group compared to the blank group. Compared with the model group, the liver LCATmRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is increased, and the difference has statistical significance (P < 0.05). Compared with western medicine group, the liver LCAT mRNA level of mice in spleen-invigorating and lipid-lowering prescription group is increased, and the difference has statistical significance (P < 0.05).

(2) SRBI: there was no statistical difference in SRBI mRNA levels between groups. The mice in the model group had a reduced tendency to have a lower liver SRBI mRNA level compared to the blank group. Compared with the model group, the liver SRBI mRNA level of the mice in the spleen-strengthening and lipid-lowering formula group has a reduced tendency.

(3) ABCA1: the liver ABCA1mRNA levels tended to be reduced in the model group compared to the blank group. Compared with the model group, the liver ABCA1mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is obviously increased, and the difference has statistical significance (P < 0.01). Compared with western medicine group, the liver ABCA1mRNA level of mice in spleen-invigorating and lipid-lowering prescription group is increased, and the difference has statistical significance (P < 0.05).

The liver LCAT, SRBI, ABCA1mRNA levels tended to be reduced in the model mice compared to the blank mice. Compared with the model group, the liver ABCA1mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is obviously increased (P < 0.01), the LCAT mRNA level is increased (P < 0.05), and the SRBI mRNA level is reduced without statistical significance. (Table 9, FIG. 12)

Table 9 comparison of LCAT, SRBI, ABCA mRNA in liver tissue of mice of each group

Note that: compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01; compared with the western medicine group, the medicine is prepared, ^& P<0.05

2.13 effects of spleen invigorating and lipid lowering formulation on cholesterol reverse transport related proteins in liver

In order to investigate the regulation and control effect of the spleen-strengthening lipid-lowering prescription on the expression of ABCA1, quantitative analysis is carried out on the expression of ABCA1 protein according to the RT-PCR experimental result. Compared with the blank group, the difference of the liver ABCA1 protein level of the mice in the model group has no statistical significance. Compared with the model group, the western medicine group and the spleen-strengthening and lipid-lowering formula group have the advantages that the liver ABCA1 protein level of the mice is obviously increased, and the differences have statistical significance (P is less than 0.01). (FIG. 13)

2.14 Effect of spleen-invigorating and lipid-lowering formulation on mRNA related to cholesterol excretion in liver

(1) ABCG5: the liver ABCG5 mRNA levels tended to be reduced in the model group compared to the blank group. Compared with the model group, the liver ABCG5 mRNA level of the mice in the spleen-strengthening lipid-lowering prescription group is increased (P < 0.05).

(2) ABCG8: the liver ABCG8 mRNA levels were decreased in the model group compared to the blank group. Compared with the model group, the liver ABCG8 mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is increased (P < 0.05).

(3) CYP7A1: compared with the blank group, the liver CYP7A 1mRNA level of the mice in the model group has a reduced tendency. Compared with the model group, the liver CYP7A 1mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is obviously increased, and the difference has statistical significance (P < 0.01).

Compared with the blank group, the liver CYP7A1, ABCG5 and ABCG8 mRNA levels of the mice in the model group have a reduced tendency. Compared with the model group, the liver CYP7A 1mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is obviously increased (P < 0.01), and the mRNA levels of the ABCG5 and the ABCG8 are increased (P < 0.05). (Table 10, FIG. 14)

TABLE 10 influence of spleen-invigorating and lipid-lowering formulations on cholesterol excretion-related mRNA in liver

Note that: compared with the model group, the method has the advantages of high accuracy, ^# P<0.05， ^## P<0.01。

2.15 Effect of the recipe for invigorating spleen and reducing lipid on cholesterol excretion-related proteins in liver

To investigate the role of the spleen-invigorating lipid-lowering formulation in regulating CYP7A1 expression, quantitative analysis of CYP7A1 protein expression was performed according to RT-PCR experimental results. Compared with the blank group, the liver CYP7A1 protein level of the mice in the model group is reduced, and the difference has statistical significance (P < 0.05). Compared with the model group, the liver CYP7A1 protein level of the mice in the spleen-strengthening and lipid-lowering prescription group is obviously increased, and the difference has statistical significance (P < 0.01). (FIG. 15)

2.16 Effect of spleen invigorating and lipid lowering formulation on cholesterol nuclear transcription factor and nuclear receptor related mRNA in liver

(1) SREBP-1: there was no statistical difference in SREBP-1mRNA levels between the groups. The mice in the model group had a reduced tendency to have a liver SREBP-1mRNA level compared to the blank group. Compared with the model group, the liver SREBP-1mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group has an ascending trend.

(2) SREBP-2: compared with the blank group, the liver SREBP-2mRNA level of the mice in the model group is significantly reduced, and the difference has statistical significance (P < 0.01). Compared with the model group, the western medicine group and the spleen-strengthening and lipid-lowering formula group have statistically significant differences (P < 0.05) in that the liver SREBP-2mRNA level of the mice is increased.

(3) LXR- α: the liver LXR- α mRNA levels were decreased in the mice of the model group compared to the blank group. Compared with the model group, the liver LXR-alpha mRNA level of the mice in the spleen-strengthening and lipid-lowering prescription group is increased (P < 0.05).

Compared with the blank group, the liver SREBP-2mRNA level of the mice in the model group is obviously reduced (P < 0.01), and the LXR-alpha mRNA level has a lower trend. Compared with the model group, the spleen-strengthening lipid-lowering formula group mice have elevated liver SREBP-2mRNA levels (P < 0.05), and LXR-alpha mRNA levels (P < 0.05), while SREBP-1mRNA has no statistical significance. (Table 11, FIG. 16)

TABLE 11 influence of spleen-invigorating and lipid-lowering formulations on cholesterol nuclear transcription factors and nuclear receptor-associated mRNAs in liver

Note that: compared with the blank group, ^* P<0.05; compared with the model group, the method has the advantages of high accuracy, ^# P<0.05

the foregoing is merely a preferred embodiment of the present invention, and it should be noted that modifications and additions may be made to those skilled in the art without departing from the method of the present invention, which modifications and additions are also to be considered as within the scope of the present invention.

Claims

1. The traditional Chinese medicine composition for treating hypercholesterolemia and/or atherosclerosis is characterized by being prepared from the following raw materials in parts by weight: 20-40 parts of astragalus membranaceus, 2-10 parts of ginseng, 9-21 parts of Chinese yam, 9-21 parts of prepared rehmannia root, 9-21 parts of poria cocos, 3-15 parts of purified pinellia tuber, 6-18 parts of dried orange peel, 6-18 parts of red sage root, 9-21 parts of Chinese angelica, 10-30 parts of rhizoma alismatis and 2-10 parts of coptis chinensis.

2. The traditional Chinese medicine composition according to claim 1, which is characterized by being prepared from the following raw materials in parts by weight: 25-35 parts of astragalus membranaceus, 4-8 parts of ginseng, 12-18 parts of Chinese yam, 12-18 parts of prepared rehmannia root, 12-18 parts of poria cocos, 6-12 parts of purified pinellia tuber, 9-15 parts of dried orange peel, 9-15 parts of red sage root, 12-18 parts of Chinese angelica, 15-25 parts of rhizoma alismatis and 4-8 parts of coptis chinensis.

3. The traditional Chinese medicine composition according to claim 2, which is characterized by being prepared from the following raw materials in parts by weight: 30 parts of astragalus, 6 parts of ginseng, 15 parts of Chinese yam, 15 parts of prepared rehmannia root, 15 parts of poria cocos, 9 parts of purified pinellia tuber, 12 parts of dried orange peel, 12 parts of red sage root, 15 parts of Chinese angelica, 20 parts of oriental waterplantain rhizome and 6 parts of coptis root.

4. A Chinese medicinal composition according to claims 1-3, wherein the dosage form of the Chinese medicinal composition is granule, tablet, capsule, oral liquid, mixture or syrup.

5. Use of a Chinese medicinal composition according to any one of claims 1-3 for the preparation of a medicament for the treatment of hypercholesterolemia and/or atherosclerosis.