miR-628促进烧伤后胰岛素抵抗和骨骼肌消耗的机制研究

项目名称： miR-628促进烧伤后胰岛素抵抗和骨骼肌消耗的机制研究

项目编号： No.81471873

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郁永辉

作者单位： 北京工商大学

项目金额： 72万元

中文摘要： 胰岛素抵抗是II型糖尿病、肥胖症、烧伤等患者的常见临床表现。而烧伤是常见的意外伤害之一，在我国烧伤是继交通事故之后导致意外死亡的第二大因素。临床研究发现，烧伤可导致患者出现胰岛素抵抗进而增加患者感染或败血症的发生率；另外，骨骼肌消耗也是烧伤患者的重要临床表现，导致机体出现严重的负氮平衡及营养不良，不利于创面愈合。近来研究发现，miRNA参与调控II型糖尿病、肥胖症等疾病中的胰岛素抵抗，而胰岛素受体底物1（IRS1）是miRNA参与胰岛素抵抗的主要作用靶点。同时，研究还显示骨骼肌细胞凋亡活性增强可能与骨骼肌消耗密切相关。目前关于miRNA与烧伤诱导的胰岛素抵抗及骨骼肌消耗的关系还未见报道。我们前期的研究发现烧伤后骨骼肌中miR-628表达升高，且IRS1是miR-628的潜在作用靶点。本课题旨在揭示miR-628抑制IRS1表达而促进胰岛素抵抗及骨骼肌细胞凋亡进而诱发骨骼肌消耗的分子机制。

中文关键词： 微小RNA-628；胰岛素受体底物1；胰岛素抵抗；细胞凋亡；骨骼肌消耗

英文摘要： Insulin resistance is the common clinical manifestation in diabetes II, obesity or burn patients. Burn injury is one of the common accidental injury. In China, burn injury, ranks only second to traffic accident, is the second factor leads to unexpected death. Clinical studies indicate that burn injury can induce insulin resistance which might result in elevating the occurance of infection and sepsis. Otherwise, skeletal muscle wasting is also the important clinical manifestation of burn patients, and induces negative nitrogen balance and malnutrition, which are disadvantageous to wound healing. Recent studies demonstrate that miRNA involved in regulating diabetes type II or obesity induced insulin resistance.Insulin receptor substrate 1 (IRS1) is the primary target of miRNA mediated insulin resistance. And further studies show that enhanced skeletal muscle cell apoptosis is closely related with skeletal muscle wasting. However, there is no report focuses on the relationship of miRNA and burn-induced insulin resistance and skeletal muscle wasting. Our latest results indicate that miR-628 is significantly increased in skeletal muscle of burned rats, and IRS1 is the potential target of miR-628. This project is aimed to reveal the molecular mechanism of miR-628 promotes burn-induced insulin resistance and skeletal muscle cell apoptosis which subsequently triggers skeletal muscle wasting via suppressing IRS1 expression.

英文关键词： miR-628;insulin receptor substrate 1;insulin resistance;cell apoptosis;skeletal muscle wasting