MicroRNA调控斑马鱼心脏损伤后再生的作用和机制

项目名称： MicroRNA调控斑马鱼心脏损伤后再生的作用和机制

项目编号： No.81470407

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： 秦永文

作者单位： 中国人民解放军第二军医大学

项目金额： 73万元

中文摘要： 成熟的心肌细胞几乎不存在分化、增殖的能力。因此，心脏在损伤情况下（如心肌梗死）不能进行自身再生修复，从而导致心脏功能的部分丢失甚至衰竭。斑马鱼心脏再生能力的发现，为进一步探究心肌细胞分化、增殖提供了研究平台，但其再生机制仍不清楚。课题组前期实验显示，成年斑马鱼心脏损伤后再生过程中多个microRNA(miRNA)的表达变化显著，干预特定miRNA对培养的斑马鱼心肌细胞增殖能力有明显影响。本研究拟：1) 通过miRNA芯片、定量PCR等方法明确斑马鱼心脏再生过程中表达明显变化的miRNA；2) 在离体和整体水平，通过基因干预的方法确定特定miRNA对心肌细胞增殖和心脏再生能力的影响；3）阐明特定miRNA在斑马鱼心脏再生过程中起关键作用的分子机制。本项目利用斑马鱼心脏再生模型深入研究miRNA在心脏损伤后修复中的作用和机制，为以特定miRNA作为干预靶点对心脏的再生修复治疗开辟一条重要的途径

中文关键词： 微小RNA；斑马鱼；心脏；再生；机制

英文摘要： Because the mature cardiomyocytes hardly exist differentiation and proliferation, the heart can not repair itself by regeneration in the face of myocardial injury, such as myocardial infarction, resulting in the loss of part of the cardiac function and even heart failure. The discovery of zebrafish heart regeneration provides a research platform for further exploring the myocardial cells differentiation and proliferation, but the underlying mechanism of zebrafish cardiac regeneration is still unclear. Our preliminary experiments showed that the expression of many kinds of miRNAs had evident change during the regeneration process after the damage of adult zebrafish heart. Intervention with specific miRNA could influence the proliferation of cultured zebrafish cardiomyocytes. Therefore, the aim of this study is to: 1) make it clear that which miRNAs' expression will change significantly in zebrafish heart regeneration process by chip analysis and quantitative PCR method; 2) observe the effect of specific miRNA on cardiomyocyte proliferation and cardiac regeneration in vitro and in vivo by knock-down and over-expression of the level of miRNAs; 3) identify the functional target gene of specific miRNA, which may play a key role in the zebrafish heart regeneration process. In-depth study of the role and mechanism of miRNAs in cardiac repair and regeneration after injury using zebrafish heart regeneration model will provide specific miRNA as an intervention target to treat heart injury for cardiac regeneration repair.

英文关键词： MicroRNA;Zebrafish;Heart;Regeneration;Mechanism