心脏干细胞源外泌体lncRNA对急性心肌梗死后心肌修复的调控机制研究

成人心脏中含有少量固有心脏干细胞（CSCs）可用于心脏修复和再生；新近研究发现，急性心肌梗死后CSCs可能是通过旁分泌机制修复受损心肌，其中含有大量非编码RNA（如microRNAs、lncRNAs）的外泌体（exosome）可能是介导旁分泌效应的重要载体。本课题组前期研究发现，心脏干细胞源exosome可减少缺氧诱导的心肌细胞凋亡，但具体机制尚不明确。因此，我们提出如下假设：心梗后的急性缺血缺氧可诱导CSCs，促使其分泌功能变异的exosome，将lncRNA等遗传信息传递至受损的心肌细胞，调控心肌细胞的抗凋亡能力，改善心肌重构。本项目拟结合基因芯片和生物信息学等筛选出心脏祖细胞源exosome中调控心肌再生修复的lncRNA，在整体动物、细胞和分子水平全面观测exosome与心肌细胞的交互作用及其调控机制。

The resident cardiac stem cells (CSC) exist in adult heart perform the restoration and regeneration of insulted heart. Recent studies indicate that injured myocardium maybe repaired by a paracrine mechanism of CSC. Exosomes ，which carry noncoding RNAs ，such as microRNAs and lncRNAs, are important mediators for the paracrine effect. Our pilot studies showed CSC derived exosomes effetiently inhibted apoptosis of cardiomyocytes although the specific mechanisms were largely not understood. So we hypothesize that the ischemic and hypoxic myocardium microenvironment after acute myocardial infarction (MI) induces CSC to secret function specific exosomes. Then lncRNAs are transported to insulted cardiomyocytes by exosomes, which reduce apoptosis and ventricular remodeling. Bioinformatics and lncRNA microarray are employed to filter out the restoration and regeneration regulating lncRNAs from exosomes. Then the regulatory mechanisms, especially the epigenetic effect of exosome on ventricular remodeling and the mutual effects between exosome and cardiomyocyte will be studied in vitro and in vivo. Our study aims at understanding the reciprocity between CSC and microenvironment .