Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis

A technology for atherosclerosis and macrophages, which is applied in the field of medicine, can solve the problems that there is no protective effect of macrophage β-arrestin, and achieve high safety effects

Inactive Publication Date: 2016-05-11
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Macrophages are the main source of foam cells in atherosclerotic plaques, however, so far, there are no reports of macrophage β-arrestin having a protective effect on atherosclerosis

Method used

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  • Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis
  • Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis
  • Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Effect of macrophage β-arrestin-1 gene on serum total cholesterol after atherosclerosis occurs.

[0028]The gene knockout method of macrophage β-arrestin-1-specific myeloid gene knockout mouse (β-arr-1fl / flLysMcre) is obtained through the Cre-Loxp recombinase system, that is, through the Cre mouse (purchased from the U.S. The Jackson Laboratory (The Jackson Laboratory, article number 004781, https: / / www.jax.org / strain / 004781) and Loxp mice (obtained from the Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, cultivated by the institute itself), were provided by the inventor's laboratory Obtained by self-mating and breeding.

[0029] 1. Construction of a mouse model of atherosclerosis

[0030] The mice after bone marrow transplantation were raised in the marked SPF environment. Give high-fat feed (Western diet) (purchased from Shanghai Proton Biotechnology Co., Ltd.), and the formula is shown in the table below. After 12 weeks of feedin...

Embodiment 2

[0039] Example 2: Effect of macrophage β-arrestin-1 gene on the overall plaque area of ​​aorta after atherosclerosis occurs.

[0040] Oil red O staining of the whole mouse aorta: the overall plaque area of ​​the aorta was detected by oil red O staining of the whole aorta. The specific implementation method is as follows: take the mouse model of atherosclerosis caused by the above method, and inject 3.5% chloral hydrate into the abdominal cavity for anesthesia. The thorax of the anesthetized mouse was opened, and the heart and aorta were taken out after perfusion with normal saline and fixed in 4% paraformaldehyde for 24 hours. The whole aorta was dissected under the operating microscope, and the aorta was cut longitudinally with micro forceps and micro scissors to expose the aortic intima, and fixed with pins. Prepare oil red O dye solution (Zhuhai Beso). The aorta with flattened intima was placed in oil red staining solution for 15 minutes, followed by 70% ethanol color sep...

Embodiment 3

[0043] Example 3: Macrophage β-arrestin-1 gene affects aortic root plaque formation in atherosclerosis.

[0044] Oil red O staining of mouse aortic root: the overall plaque area of ​​aorta was detected by oil red O staining of aortic root. The specific implementation method is as follows: take the mouse model of atherosclerosis caused by the above method, and inject 3.5% chloral hydrate into the abdominal cavity for anesthesia. The thorax of the anesthetized mouse was opened, and the heart and aorta were taken out after perfusion with normal saline and fixed in 4% paraformaldehyde for 24 hours. The mouse aortic root (at the aortic valve) was made into a frozen section with a thickness of 10 μm using a cryostat (purchased from Leica). Prepare oil red O staining solution. The frozen sections were washed in water for 30 seconds, wiped dry, and placed in oil red staining solution for 15 minutes, followed by 60% ethanol color separation for 1 minute and water washing for 1 minute...

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Abstract

The invention relates to the technical field of medicine, and provides new application of macrophage beta-profilin-1, namely application of macrophage beta-profilin-1 to preparation of a drug for preventing or treating atherosclerosis. It is proved through experiments that in comparison with wild type mice, the serum total cholesterol content of macrophage beta-arrestin-1 specificity myelogenous knockout mice is remarkably increased, and it is found through oil red O dyeing that the aorta overall plaque area and the plaque area of aorta roots are obviously increased compared with those of the wild type mice. By changing the macrophage beta-arrestin-1 gene expression level through virus transfection, and it is found that macrophage phagocytosis lipid is increased by interfering beta-arrestin-1 expression and is decreased by overexpressing beta-arrestin-1. The results show that the beta-arrestin-1 gene has a protective effect on the severity degree and prognosis of atherosclerosis.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of macrophage beta-arrestin-1 in the preparation of drugs for preventing or treating atherosclerosis. Background technique [0002] β-arrestins (β-arrestins) are a group of multifunctional small molecular proteins, which play a very important role in regulating intracellular signal transduction. Its classic role is to participate in the desensitization and endocytosis of G protein-coupled receptors (References 1. Shenoy SK, Lefkowitz RJ. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci 2011; 32:521-533.). [0003] Recent studies have found that β-arrestins, especially β-arrestin-1 protein, as a "traffic member" of signal transduction, is also involved in many non-G protein-coupled receptor-activated signal transduction, in proteasome degradation, apoptosis And play an important role in a variety of cell signal transduction (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K48/00A61P9/10
CPCA61K38/1709A61K48/00
Inventor 刘冲邵柏棕柯苹徐哲琦苏定冯
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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