ENaC and application of inhibitor thereof in preventing, alleviating and/or treating atherosclerosis
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An atherosclerosis and inhibitor technology, applied in the field of medicine, can solve problems such as unsatisfactory treatment and control effects
Active Publication Date: 2019-02-22
HARBIN MEDICAL UNIVERSITY
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The occurrence of atherosclerosis is the result of the joint action of multiple factors. Many risk factors for atherosclerosis have been discovered so far, but the treatment and control effects are not satisfactory. Lipid lowering and anti-inflammatory treatment are currently the most important treatment measures
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Embodiment 1
[0027] Embodiment 1 mouse atherosclerosis model (AS) obtains
[0028] 1. Grouping of experimental animals: male LDLR- / - mice aged 8 weeks, weighing 19-25g, and γ-ENaC - / - LDLR - / - Double gene knockout mice were fed high-fat diet (HFD) and low-fat diet (NC) respectively, and were divided into LDLR - / - HFD group, LDLR - / - NC group, γ-ENaC - / - LDLR - / - HFD group, γ-ENaC - / - LDLR - / - NC group, LDLR - / - HFD administration of amiloride (Amiloride) group, LDLR - / - There were 6 groups in the NC gavage amiloride group, 20 rats in each group.
[0029] 2. Atherosclerosis model induced by high fat operating procedures
[0030] Knockout of the LDLR gene (LDLR - / - ) mice with γ-ENaC - / - LDLR - / - Double gene knockout mice were used to establish AS models, and phenotype correlation analysis was performed to clarify the role of ENaC gene in atherosclerotic diseases. From the age of 8 weeks, the mice in the HFD group were sacrificed after being fed with a high-fat diet for 16 weeks...
Embodiment 2A
[0031] Embodiment 2 AS model mouse plaque area measurement
[0032] 1. Final mouse tissue collection
[0033] 1) Execute the mice of the 6 groups in Example 1, and carefully remove the aorta from the root of the aorta to the bifurcation of the common iliac artery;
[0034] 2) Separate all adventitia and fat under a stereomicroscope;
[0035] 3) Fix the separated blood vessels in 4% neutral formaldehyde, and put them in a 4oC refrigerator overnight;
[0036] 4) Take out the aorta and use ddH 2 O wash 3 times, each 5min, to remove the attached formaldehyde solution;
[0037] 5) Dissect the blood vessel longitudinally under a stereomicroscope;
[0038] 6) Use liquid with oil red (reserve liquid: ddH 2 O=3:2), after standing for 10min, it can be used;
[0039] 7) The aorta was placed in oil red staining solution, and dipped for 2 hours at room temperature;
[0040] 8) Discard the staining solution, wash the staining solution with 70% alcohol until the blood vessel wall appe...
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Abstract
The invention discloses an ENaC and an application of an inhibitor thereof in preventing, alleviating and / or treating atherosclerosis and belongs to the technical field of medicines. By taking a LDL- / -mouse and gamma-ENaC- / -LDLR- / - as experimental objects, a high fat diet-induced atherosclerosis model is obtained, and the result shows that compared with the LDLR- / - mouse, the plaque area of the aorta of the mouse without the ENaC gene or inhibiting the ENaC gene is reduced obviously. The ENaC plays roles of promoting plaque formation of aorta and promoting atherosclerosis. According to the functions of the ENaC, the invention provides the application of the ENaC as a medicine target in a medicine for preventing, alleviating and / or treating atherosclerosis and an application of the inhibitor of ENaC in preparing a medicine for preventing, alleviating and / or treating atherosclerosis. The invention provides a novel target and a medicine for preventing, alleviating and / or treating atherosclerosis, and has important meaning in illuminating the molecular mechanism of genesis and development processes of atherosclerosis and searching for the molecular target for atherosclerosis treatment.
Description
technical field [0001] The invention relates to a new target for treating atherosclerosis and its medicine, in particular to the application of ENaC and its inhibitor in the preparation of medicines for preventing, alleviating and / or treating atherosclerosis. The invention belongs to the technical field of medicine. Background technique [0002] In recent years, the incidence of major cardiovascular diseases in my country, including hypertension, coronary heart disease and peripheral vascular diseases, has increased significantly. Epidemiological surveys show that there are as many as 230 million patients with cardiovascular diseases in my country. In 2010, 580 million people in China had at least one risk factor related to cardiovascular disease. If the corresponding basic research and clinical interventions are not improved, the risk of cardiovascular disease will increase by 50% by 2030. At present, cardiovascular and cerebrovascular diseases are the leading cause of de...
Claims
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