miR-30c负向调控ACTC1抑制心房纤维化降低房颤易感性的研究

项目名称： miR-30c负向调控ACTC1抑制心房纤维化降低房颤易感性的研究

项目编号： No.81500260

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘海

作者单位： 郑州大学

项目金额： 18万元

中文摘要： 心房颤动(房颤)是临床最常见的持续性心律失常，但其机制仍未阐明。在前期研究中，我们联合应用miRNA芯片、蛋白组学、生物信息学技术，发现一个可能参与房颤机制的miR-30c/ACTC1调控通路。依据最新研究进展和预实验结果我们提出miR-30c通过负向调控ACTC1抑制心房纤维化从而降低房颤易感性的科学假说。为验证假说，本项目选择临床标本、犬/小鼠房颤模型以及心房成纤维细胞模型；应用基因转染、转基因、基因敲除技术手段，实现过表达及抑制表达miR-30c；使用电生理学、形态学、分子生物学多种检测方法，观察miR-30c对心房纤维化及房颤易感性的影响；从分子—细胞—整体水平、体外—体内实验，多层次、多角度阐明miR-30c负向调控ACTC1抑制心房纤维化降低房颤易感性的作用及其分子机制。本项目的实施，将为进一步揭示房颤机制提供新理论，并为下一步的房颤防治提供新思路和新靶点。

中文关键词： 心房颤动；心房纤维化；心房结构重构；微小RNA；ACTC1

英文摘要： Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice, but its mechanism is still unclear. In preliminary study, we found the miR-30c/ACTC1 pathway maybe involve in the mechanism of AF combined using the miRNA microarray,proteomics and bioinformatics technology. According to the latest research progress and results of preliminary experiments, we raise a scientific hypothesis that miR-30c inhibit atrial fibrosis to reduce AF vulnerability by negatively regulating ACTC1. In order to verify the hypothesis, This study aims to select clinical specimens, dog/mice AF model, atrial fibroblasts model; using gene transfection, gene transfer and gene knockout technology; realizing overexpression of miR-30c and inhibition of miR-30c expression; observing the effect of miR-30c on atrial fibrosis and AF vulnerability by using the method of electrophysiology,morphology and molecular biology; to clarify the effect and molecular mechanism that miR-30c inhibit atrial fibrosis to reduce AF vulnerability by negatively regulating ACTC1 from the molecular -cell- organ level, in vitro and in vivo experiment, different levels and perspectives. This study may provide new insights into the underlying mechanisms of AF and provide potential novel mechanism-based therapeutic strategies for AF.

英文关键词： atrial fibrillation;atrial fibrosis;atrial structural remodeling;microRNA;ACTC1