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Use of SIRT1 in preparation of drugs for prevention of diseases caused by endothelial dysfunction

A technology of 1. SIRT1 and uses, which is applied in the field of use of SIRT1 in the preparation of drugs for preventing diseases caused by endothelial cell dysfunction, and can solve the problems of lack of increasing vascular endothelial oxidative stress level, endothelial dysfunction, shortening lifespan and the like

Active Publication Date: 2012-05-16
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Overexpression of genes encoding superoxide dismutase and catalase can prolong the lifespan of Drosophila, while knocking out the gene encoding superoxide dismutase can shorten its lifespan; MnSOD deficiency increases the level of oxidative stress in the vascular endothelium, leading to endothelial dysfunction

Method used

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  • Use of SIRT1 in preparation of drugs for prevention of diseases caused by endothelial dysfunction
  • Use of SIRT1 in preparation of drugs for prevention of diseases caused by endothelial dysfunction
  • Use of SIRT1 in preparation of drugs for prevention of diseases caused by endothelial dysfunction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Detection of SIRT1 expression level changes in human umbilical vein endothelial cells stimulated by high glucose by realtime PCR

[0031] In order to preliminarily explore the role of SIRT1 in high glucose-induced endothelial dysfunction, the following experiments were carried out.

[0032] 1. Obtain and culture human umbilical vein cells by conventional methods. The method is briefly described as follows: the umbilical cord of the newborn was taken to obtain the umbilical vein, and after necessary treatment, human umbilical vein endothelial cells (HUVEC) were obtained by perfusing IV collagenase and incubated at 37°C. The obtained HUVEC cells were cultured in medium M200 (purchased from Cascade Biologics Inc., Portland, Oregon, USA., M-200-500) and cultured and subcultured according to conventional primary cell culture methods;

[0033] 2. Extract RNA according to the standard RNA extraction method in the second edition of "Molecular Cloning" and perform RT-...

Embodiment 2

[0041] Example 2 Effects of overexpression and interference of SIRT1 on the expression levels of p66shc, MnSOD, and PAI-1 under high glucose stimulation

[0042] Decreasing the level of p66shc can reduce the level of oxidative stress and prevent the occurrence of endothelial cell dysfunction caused by high glucose; PAI-1 is considered as a marker molecule of endothelial function, and its increased expression indicates endothelial dysfunction. MnSOD is related to the scavenging of oxygen free radicals, and the increase of its level indicates that the cells have a strong ability to resist oxidative stress. In order to verify whether SIRT1 can prevent the occurrence of endothelial cell dysfunction caused by high glucose at the cellular level, the effects of SIRT1 on the expression of p66shc, PAI-1 and MnSOD were observed by using SIRT1 overexpression and interference methods, and the positive and negative aspects of SIRT1 were verified. A role in preventing high glucose-induced e...

Embodiment 3

[0058] The expression level of SIRT1 in the C57 mouse aorta of embodiment 3 diabetes reduces

[0059] The present invention studies the expression of SIRT1 in the arteries of diabetic mice by constructing a type I diabetic mouse model and whether SIRT1 plays a protective role in the process of diabetic blood vessel damage. The method is briefly described as follows.

[0060] 1, STZ intraperitoneal injection method to construct type I diabetes model, detailed method see J.Clin.Invest.112: 725-735 (2003) (it is incorporated herein by reference in its entirety), STZ purchased from (Sigma-Aldrich, S0130) ;

[0061] 2. For protein extraction and western blot, see the relevant part of the second edition of "Molecular Cloning" for details. The antibodies used in the experiments were anti-SIRT1 (Upstate, 07-131) and anti-actin (Sigma, A5376).

[0062] Experimental results: C57 / BJ mice (purchased from the Animal Center of the Chinese Academy of Military Medical Sciences) were inject...

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Abstract

The present invention relates to a use of sirtuin 1 (SIRT1) in preparation of drugs for prevention of diseases caused by endothelial dysfunction. Specifically, the present invention relates to a use of the SIRT1 in preparation of drugs for prevention and / or treatment of endothelial dysfunctions of mammals including human, and prevention and / or treatment of diabetic vascular complications of mammals including human.

Description

technical field [0001] The present invention relates to the use of SIRT1 in the preparation of drugs for preventing and / or treating endothelial cell dysfunction in mammals including humans, and preventing / or treating diabetic vascular complications in mammals including humans. Background technique [0002] Diabetes mellitus is a chronic metabolic disease characterized by inherited or acquired defects in insulin secretion or action. This defect leads to elevated blood sugar, which in turn damages the circulatory system as well as other target organs of diabetes, such as the retina, kidneys and nervous system. Currently, the number of people suffering from diabetes is increasing rapidly. According to the statistics of the World Health Organization, in 2000, there were about 150 million diabetic patients in the world, and it is estimated that by 2010, this number will rise to 220 million (Zimmet et al., 2001). Therefore, diabetes and its complications have become a very serio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/43A61K9/00A61P3/10A61P9/00A61P9/10A61P13/12A61P25/00
Inventor 刘德培周爽陈厚早万言珍
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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