mir-17-92调节心律失常的功能及机理研究

The cardiac arrhythmia, one of the most common cardiac diseases, is a leading cause of death worldwide. It is extremely critical to elucidate molecular mechanisms of epigenetic regulation of cardiac arrhythmia, in order to develop efficient therapies. We found that miR-17-92 deficiency mice are susceptible to atrial fibrillation, the most common adult cardiac arrhythmia. This is the first study of function of miR-17-92 in cardiac conduction system and we aim to dissect the critical role of miR-17-92 in cardiac arrhythmia. We plan to investigate the following four aims using animal model, human sample and molecular studies: ①investigate the functional results of cardiac conduction system-specific knockout of miR-17-92; ②investigate the correlation between miR-17-92 expression level and cardiac arrhythmia in patients; ③investigate the efficiency of miR-17-92 treatment to reverse or control cardiac arrhythmia; ④investigate the molecular mechanisms of that how miR-17-92 maintains homeostasis of cardiac conduction system and normal heart rhythm. This study will elucidate the role of miR-17-92 in cardiac arrhythmia, and molecular mechanism of maintaining cardiac conduction system homeostasis and normal heart rhythm, to help the development of novel therapy of cardiac arrhythmia.

心律失常是最常见的心血管疾病之一，也是导致死亡的主要原因之一。研究心律失常的表观遗传调控从而寻求有效的预防和治疗，具有极其重要的科学价值和社会意义。我们的前期研究发现miR-17-92基因敲除可导致小鼠患房颤（最常见的成年心律失常）的易感性增加。本课题是首次在心脏传导系统特异性研究miR-17-92 功能，拟从动物、人和细胞及分子水平进行以下4个方面的研究系统阐述miR-17-92在心律失常中的重要作用：①研究心脏传导系统特异性miR-17-92基因敲除对心律的影响；②研究miR-17-92的表达水平与患者心律失常的相关性；③研究miR-17-92对治疗（逆转或控制）心律失常的作用；④研究miR-17-92维持心脏传导系统稳态和正常心律的分子机制。本研究将系统阐明miR-17-92在心律失常中的作用, 以及维持心脏传导系统稳态和正常心律的分子机制，从而帮助发现治疗或改良心律失常的新方法。