Sirt3基因在调节胰岛素抵抗小鼠卵母细胞线粒体功能和氧化应激损伤中的作用及其机制研究

项目名称： Sirt3基因在调节胰岛素抵抗小鼠卵母细胞线粒体功能和氧化应激损伤中的作用及其机制研究

项目编号： No.81200421

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 欧湘红

作者单位： 南方医科大学

项目金额： 23万元

中文摘要： 高胰岛素血症和胰岛素抵抗是导致女性生育力下降的重要致病因素之一。卵子质量下降所导致的胚胎发育潜能的改变是其主要原因，进一步探讨其发病机制对临床治疗该疾病具有重要的意义。本项目通过在前期已建好的模拟临床不孕症中高发病率的高胰岛素血症和胰岛素抵抗但血糖正常的小鼠疾病模型的基础上探讨：1）高胰岛素血症对小鼠卵母细胞、卵丘和颗粒细胞线粒体功能和氧化应激的损伤；2）高胰岛素血症对卵母细胞和卵丘细胞的胰岛素信号通路影响和调节；3）Sirt3是否通过影响胰岛素信号通路参与对卵母细胞质量的损伤。研究成果将为临床防治高胰岛素血症和胰岛素抵抗并不孕的妇女提供理论依据和治疗靶点。

中文关键词： 胰岛素抵抗；卵母细胞；线粒体；氧化应激；沉默信息调控子3

英文摘要： The incidence of obesity overlapped with hyperinsulinism and insulin resistance is increasing, and this linked to infertility and poor reproductive outcome. Therefore, the relationship between the metabolic syndrome and reproductive dysfunction is an active area of study, which is increasingly puzzling the infertile female. Maternal hyperinsulinism and insulin resistance impaires oocyte quality and the embryo developmental potentiality, which is one of the main reasons for female infertility. The incidence of infertility with hyperinsulinism and insulin resistance but with normal serum glucose is common. So we established successfully the disease model with hyperinsulinism and insulin resistance but normal serum glucose. On the basis of this model, we will explore whether insulin resistance disrupts the mitochondrial function of mouse oocyte, cumulus and granulosa cells, and results in the oxidative stress. Furthermore, we will study how hyperinsulinism disrupts oocyte quality through affecting the insulin signals and how Sirt3 affects the insulin signals in oocyte and cumulus cell in insulin-resistant mouse. The research is expected to provide basis and targets for preventing and treating the infertile female with insulin resistance.

英文关键词： insulin resistance；oocyte；mitochondria；oxidance stress；Sirt3