微小RNA-222与运动诱导的生理性心肌肥大的关系

项目名称： 微小RNA-222与运动诱导的生理性心肌肥大的关系

项目编号： No.81200169

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 肖俊杰

作者单位： 同济大学

项目金额： 24万元

中文摘要： 心肌肥大包括生理性和病理性二种。病理性心肌肥大常导致心力衰竭和猝死，而生理性心肌肥大却对心血管疾病有保护效应。微小RNA是基因表达和调控的控制中心之一。我们的研究提示微小RNA-222在生理性心肌肥大显著升高（包括游泳诱导和跑步诱导的生理性心肌肥大），而在病理性心肌肥大却没有变化。微小RNA-222显著地促进了心肌细胞的增殖，抑制该微小RNA阻止了游泳诱导的生理性心肌肥大。本课题拟在此基础之上，结合微小RNA-222功能缺失性实验（微小RNA-222抑制剂）和功能获得性实验（腺病毒伴随病毒-9），明确其与生理性心肌肥大的关系。然后借助基因芯片、生物信息学分析、荧光素酶实验和免疫印迹法揭示微小RNA-222介导生理性心肌肥大的分子基础。最后探索增加微小RNA-222是否可以阻止心力衰竭的发生。本研究可能发现一个介导运动诱导的生理性心肌肥大发生的关键微小RNA，为心力衰竭的干预提供新的靶点。

中文关键词： 运动；生理性肥大；微小RNA；心室重构；

英文摘要： Cardiac hypertrophy has been generally defined as either physiological or pathological. Pathological hypertrophy is often associated with increased risk of heart failure and sudden death while physiological hypertrophy is generally thought to be a benign adaptation. MicroRNAs (miRNAs, miRs) have emerged as key components of post-transcriptional gene regulators, participating in a wide range of biological processes. Our preliminary data have indicated that miR-222 was elevated in both swimmming and voluntary wheel running-induced physiological hypertrophy while remained unchanged in pathological hypertrophy. Moreover, increased miR-222 promoted cardiomyocytes proliferation and was required for swimming-induced physiological hypertrophy. Based on these finding, firstly, we will claify the role of miR-222 in physiological hypertrophy through in vivo loss-of-function (locked nucleic acid modified miR-222 inhibitor) and gain-of-function (Adeno-associated virus serotype-9, AAV-9) experiment. Secondly, combined gene array, bioinformatic analysis, luciferase reporter assay and Western Blot, the target genes of miR-222 will be identified. Finally, if elevated miR-222 is protective for heart failure will also be tested in vivo. This study will identify a critical miRNA contributing to exercise-induced physiological hyp

英文关键词： Exercise；Physiological hypertrophy；MicroRNA；Ventricular remodeling；