HDAC6介导的乙酰化表观遗传修饰在PCOS胰岛素抵抗中的作用机制

项目名称： HDAC6介导的乙酰化表观遗传修饰在PCOS胰岛素抵抗中的作用机制

项目编号： No.81200420

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： 初永丽

作者单位： 青岛大学

项目金额： 25万元

中文摘要： 多囊卵巢综合征（polycystic ovary syndrome，PCOS）是育龄期妇女最常见的内分泌紊乱疾病，也是导致女性不孕症最常见的原因之一，但发病机制目前尚不明确。越来越多的研究表明，胰岛素抵抗 (insulin resistance, IR) 和随之引起的代偿性高胰岛素血症是PCOS的主要病理生理改变。同时，表观遗传修饰在PCOS的发病机制中起到重要的作用，其中乙酰化修饰是基因转录调控的重要机制。我们在前期工作中首次证实去乙酰化酶HDAC6在PCOS病人的卵巢组织表达显著升高，提示其在PCOS中可能起重要作用。本课题将探索构筑转化医学研究模式，从参与组蛋白乙酰化的HDACs家族入手，通过细胞模型、动物模型及临床标本，对HDAC家族中的HDAC6在PCOSIR的作用及分子机制进行深入研究并提出干预策略；本课题将充实并完善PCOS发生发展的分子机制，为其防治提供新的靶点和思路。

中文关键词： 多囊卵巢综合征；胰岛素抵抗；乙酰化；；

英文摘要： Polycystic ovary syndrome (PCOS) is the most common gynecological endocrine disease among women of reproductive age, and also the major cause of anovulatory infertility. But the pathogenesis of PCOS remains unknown. More and more studies indicated that insulin resistance (IR) and the following compensatory hyperinsulinemia are the major pathophysiological changes in PCOS. At the same time, the epigenetic modification plays an important role in the pathogenesis of PCOS. Such asacetylation which playing an important role during the regulative progress of genes transcription. In our preparatory work, we confirmed for the first time that the expression of deacetylase HDAC6 in the ovaries of PCOS patients were increased remarkably and presumed that HDAC6 might play an important role in the pathogenesis of PCOS. This project will construct the translational medicine model by starting with the HDACs family in PCOS. That is, we will research the role of HDAC6 (an immportant member of HDAC family) in the pathogenesis of insulin resistance on different systems: cell models, animal models and clinical samples. It will enrich and improve the molecular pathogenesis of PCOS, and would supply new targets or ideas for preventing and treating this disease.

英文关键词： polycystic ovary syndrome；insulin resistance；deacetylase；；