睾酮缺乏致房颤易损基质（电重构和间质纤维化）的形成与microRNA调控机制

项目名称： 睾酮缺乏致房颤易损基质（电重构和间质纤维化）的形成与microRNA调控机制

项目编号： No.81470463

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： 潘振伟

作者单位： 哈尔滨医科大学

项目金额： 73万元

中文摘要： 睾酮缺乏是临床上房颤发生的主要危险因素之一，但其具体作用与机制仍不明。心房离子通道重构和间质纤维化是房颤发生的易损基质；microRNAs在心脏离子通道重构和纤维化过程中起关键调控作用。我们最新研究发现miRNA也是房颤发生的关键调控分子（Circulation 2010；JCI，2013）。因此，我们假设：睾酮缺乏通过miRNA途径致房颤的易损基质（电重构、间质纤维化）形成。本项目将研究：1）睾酮缺乏对心房离子通道重构、间质纤维化和房颤的影响；2）睾酮缺乏时表达变化的miRNA（miR-1、miR-26和miR-328）在睾酮调节离子通道重构和房颤发生中的作用；3）睾酮缺乏时表达变化miRNA（miR-26、miR-29和miR-30）在睾酮调节心房纤维化和房颤发生中的作用。本研究将加深我们对睾酮缺乏与房颤发生及miRNA调控作用的认识，为临床上睾酮的替代治疗提供理论依据。

中文关键词： 心房颤动；离子通道；电重构；心房纤维化；微小RNA

英文摘要： Testosterone deficiency represents a risk factor of atrial fibrillation(AF) clinically, but the direct effect of testosterone deficiency on the occurrence of AF and the underlying mechanism remain unclear. The main pathological basis for AF susceptibility is the ionic remodeling and interstitial fibrosis. MicroRNAs have been demonstrated to be critical regulators of ionic remodeling and interstitial fibrosis. We recently found that miRNAs play important role in the development of AF(Circulation, 2010;JCI, 2013). Therefore, we hypothesized that testosterone deficiency increased AF susceptibility through miRNA regulated ionic remodeling and interstitial fibrosis. In this project we will explore: 1) The effect of testosterone deficiency on ionic remodeling, interstitial fibrosis and AF susceptibility; 2) The role of arrhythmia-related miRNAs (miR-1, miR-26、miR-328), which have been shown to be up-regulated during testosterone deficiency, in the development of ionic remodeling and AF; 3) The role of fibrosis-related miRNAs (miR-26、miR-29, miR-30), which have been shown to be down-regulated during testosterone deficiency, in the development of interstitial fibrosis and AF. This project will improve our understanding of the effect of testosterone deficiency on the susceptibility of AF and the regulatory role of miRNA, which will help building the theoretical basis for the application of testosterone replacement therapy clinically.

英文关键词： Atrial fibrillation;Ion channel;Electric remodeling;Atrial fibrosis;microRNA