Application of taurocholic acid in preparation of medicine for preventing and / or treating atherosclerosis

Abstract

The invention discloses application of taurocholic acid in preparation of a medicine for preventing and / or treating atherosclerosis, and belongs to the field of biological medicine. The taurocholic acid can reduce the area of atheromatous plaques of the aorta and aorta root of a mouse and regulate the blood lipid level of the mouse. Animal experiment results prove that taurocholic acid has prevention and improvement effects on aortic atheromatous plaque formation of atherosclerotic mice. The medicine disclosed by the invention is relatively low in toxicity and relatively high in safety.

Description

Technical Field

[0001] The invention relates to the application of taurolithocholic acid in preparing a medicine for preventing and / or treating atherosclerosis, and belongs to the field of biomedicine. Background Art

[0002] Cardiovascular and cerebrovascular diseases are a general term for cardiovascular and cerebrovascular diseases. They are characterized by high morbidity, high disability and high mortality, and seriously threaten the health and safety of middle-aged and elderly people. Atherosclerosis is the main pathological basis of cardiovascular and cerebrovascular diseases, and is a chronic low-grade inflammatory disease accompanied by lipid metabolism disorders. Hyperlipidemia, aging, diabetes, obesity, etc. are well-known traditional risk factors for atherosclerosis. Atherosclerosis is characterized by vascular cell dysfunction and accumulation of low-density lipoprotein particles in plaques. Changes in the levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol caused by abnormal lipid metabolism are one of the main mechanisms for the occurrence and development of atherosclerosis.

[0003] Atherosclerosis is a chronic disease with no obvious symptoms in the early stage. As blood vessels narrow and different organs are affected, corresponding ischemic symptoms such as dizziness, headache, chest tightness, and chest pain will appear. At present, the commonly used lipid-lowering drugs for the treatment of atherosclerosis in clinic are statins and fibrates, but statins can cause fatigue, muscle pain, abnormal muscle enzymes and liver enzymes, while fibrates can cause nausea, vomiting, abdominal distension, headache, insomnia and other adverse reactions. Therefore, it is particularly important to find and develop safe and effective anti-atherosclerotic drugs.

[0004] Bile acids are the main components of bile. They are synthesized in the liver from cholesterol, stored in the gallbladder, and secreted into the intestines with eating activities. They promote the absorption of lipids and fat-soluble vitamins and regulate liver function. Bile acids are key regulatory factors in the metabolic network. They are not only involved in lipid digestion and absorption, but also potential therapeutic targets for metabolic disorders. Taurolithocholic acid was originally discovered in bovine bile and bovine gallstones. It is a secondary bile acid derived from the primary bile acid chenodeoxycholic acid. Currently, taurolithocholic acid is widely studied and used to promote cholesterol metabolism. On the one hand, sodium taurolithocholic acid can promote the excretion of cholesterol and regulate the balance of cholesterol synthesis. On the other hand, sodium taurolithocholic acid also has antioxidant and anti-inflammatory effects.

[0005] So far, there has been no report on the application of intestinal flora in the preparation of taurolithocholic acid for the prevention and treatment of atherosclerosis. Summary of the invention

[0006] Technical problem: The technical problem to be solved by the present invention is to provide the application of taurolithocholic acid in the preparation of drugs for preventing and / or treating atherosclerosis.

[0007] Technical solution: To achieve the above-mentioned purpose, the present invention provides the following technical solution: the use of taurolithocholic acid in the preparation of a drug for preventing and / or treating atherosclerosis, wherein the structural formula of the taurolithocholic acid is shown in formula (I):

[0008]

[0009] The preferred technical solution is: taurolithocholic acid is prepared with auxiliary materials of corresponding dosage forms into oral liquid, injection, tablet, pill, dispersant, capsule, dripping pill, granule, suspension and emulsion.

[0010] Taurolithocholic acid can also be used as a health supplement to prevent atherosclerosis.

[0011] Beneficial effects: The present invention provides a taurolithocholic acid preparation having preventive and therapeutic effects on atherosclerosis. The present invention has the following obvious progress and advantages:

[0012] Through pharmacological experiments on classic animal models of atherosclerosis, the results showed that taurolithocholic acid can significantly reduce plasma total cholesterol, triglycerides and low-density lipoprotein levels, increase high-density lipoprotein levels, improve the deposition of atherosclerotic plaques in the aorta and aortic root of mice, and inhibit the formation of atherosclerotic plaques. The experimental results prove that taurolithocholic acid has preventive and therapeutic effects on atherosclerosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 The results of plasma total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein concentrations in the control group, model group, taurolithocholic acid group and atorvastatin group; * P<0.05, ** P<0.01, *** P<0.001 compared with the model group.

[0014] Figure 2 Oil red O staining results of aortic root atherosclerotic plaques in the control group, model group, taurolithocholic acid group, and atorvastatin group; * P<0.05, ** P<0.01, *** P<0.001 compared with the model group.

[0015] Figure 3 The results of macroscopic Oil Red O staining of aorta in the control group, model group, taurolithocholic acid group, and atorvastatin group; * P<0.05, ** P<0.01, *** P<0.001 compared with the model group. DETAILED DESCRIPTION

[0016] The following specific examples illustrate the implementation of the present invention. The contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0017] Example 1: Effects of taurolithocholic acid on blood lipids and aortic plaque formation in atherosclerosis model mice.

[0018] 1. Experimental Animals: ApoE - / - Mice, 5-7 weeks, male.

[0019] 2. Drug preparation: Tablets for the treatment and prevention of atherosclerosis with a taurolithocholic acid content of 10 mg / tablet are selected (except taurolithocholic acid, the other ingredients are conventional excipients for preparing tablets, such as starch, powdered sugar, lactose, dextrin, maltodextrin and compressible starch), ultrasonically dispersed in 0.5% sodium carboxymethyl cellulose (CMC-Na), and used for oral administration, with a dosage of 10 mg / kg.

[0020] 3. Experimental methods:

[0021] (1) Grouping and treatment: After the animals were adapted to the environment for 1 week, the mice were divided into a control group, a model group, a taurolithocholic acid group, and an atorvastatin group, with 8 mice in each group. The control group was given a normal diet. The model group, the taurolithocholic acid group, and the atorvastatin group were given a high-fat diet. While the model was being established, the taurolithocholic acid group and the atorvastatin group were gavaged with 10 mg / kg daily. The control group and the model group were gavaged with an equal volume of 0.5% sodium carboxymethylcellulose daily. The duration of drug administration and the model establishment was 16 weeks.

[0022] (2) Collecting blood samples: The eyeballs were removed to collect blood, and the blood samples were placed in anticoagulant tubes for testing four plasma indicators: low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides.

[0023] (3) The animals were killed on an ice table and the aorta and heart were separated: the aorta was fixed on paraffin, stained with Oil Red O and then differentiated with 70% alcohol, the heart was embedded in OCT and then sliced ​​in a frozen centrifuge (8 μM), stained with Oil Red O, adjusted with 60% isopropanol, counterstained with hematoxylin, differentiated with hydrochloric acid alcohol, and blued with running water. The atheromatous plaques in the aorta and aortic root were observed under a microscope, and the percentage of the gross aortic plaque area to the total intima area and the atheromatous plaque area of ​​the aortic root were calculated using Image J software.

[0024] 4 Experimental results:

[0025] like Figure 1 As shown: Compared with the control group, ApoE - / -The concentrations of total cholesterol, triglycerides and low-density lipoprotein in mouse plasma increased significantly, while the concentration of high-density lipoprotein decreased significantly. Compared with the model group, taurolithocholic acid can significantly reduce ApoE - / - The levels of total cholesterol, triglycerides and low-density lipoprotein in mouse plasma were reduced, and the level of high-density lipoprotein was increased, indicating that taurolithocholic acid can significantly improve dyslipidemia caused by a high-fat diet.

[0026] like Figure 2 As shown: Compared with the control group, ApoE - / - The area of ​​atheromatous plaques in the aortic root of mice increased significantly, indicating that the atherosclerosis mouse model was successfully established. Compared with the model group, the area of ​​atheromatous plaques in the aortic root of mice in the taurolithocholic acid group was significantly reduced. This indicates that taurolithocholic acid can significantly reduce the formation of aortic root plaques in atherosclerotic mice.

[0027] like Figure 3 As shown: Compared with the control group, ApoE - / - The percentage of aortic atherosclerosis plaque area in the total aortic intima area of ​​mice increased significantly, which further proved that the atherosclerosis mouse model was successfully established. Compared with the model group, the percentage of aortic atherosclerosis plaque area in the taurolithocholic acid group mice decreased significantly. This shows that taurolithocholic acid can significantly reduce the formation of aortic plaques in atherosclerotic mice.

Claims

1. Application of taurolithocholic acid in the preparation of drugs for preventing and treating atherosclerosis.

2. Application of taurolithocholic acid in the preparation of drugs for preventing atherosclerosis.

3. Application of taurolithocholic acid in the preparation of drugs for the treatment of atherosclerosis.

4. The use according to any one of claims 1 to 3, characterized in that: Taurolithocholic acid is prepared with auxiliary materials of corresponding dosage forms into oral liquid, injection, tablet, pill, dispersant, capsule, dripping pill, granule, suspension and emulsion.

5. A pharmaceutical composition for preventing and / or treating atherosclerosis, characterized in that: It includes taurolithocholic acid and pharmaceutically acceptable salts thereof.

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