运动锻炼刺激肾脏分泌ELABELA促进心梗小鼠心肌血管新生抑制心肌纤维化及其机制研究

心血管疾病患病率和死亡率逐年上升，其中心肌梗死占比甚高，是临床医学和康复医学的重大课题。运动促进心血管疾病康复、远隔器官对心功能的影响备受关注。心源性ELABELA（ELA）含量极低，肾脏是分泌ELA的主要器官并可释放进入循环，心肌存在ELA受体。研究发现ELA具有心血管保护作用，但运动是否可刺激肾脏ELA分泌产生远隔器官—心梗心脏保护效应，目前研究尚属空白。本项目旨在探索运动刺激肾源性ELA对心梗心肌血管新生和心肌纤维化抑制的作用及其机制。拟采用在体动物实验，通过重组蛋白构建体内注射，发现ELA在有氧运动和抗阻运动刺激心梗心肌血管新生及心肌纤维化抑制中的作用；拟通过GFP标记的腺相关病毒载体导入，确定运动刺激肾脏ELA是否经循环至心脏发挥保护作用；拟通过体外细胞实验，探究ELA在运动促进心梗心肌血管新生及心肌纤维化抑制中的分子机制。本研究将为缺血心脏康复手段及其靶点筛选提供实验依据。

The morbidity and mortality of cardiovascular diseases are increasing year by year. The proportion of myocardial infarction (MI) is very high, and it has become an important subject in clinical and rehabilitation medicine. Exercise promoting the recovery of cardiovascular diseases and the effect of distant organs on cardiac function has attracted much attention. The content of heart-derived ELABELA (ELA) is extremely low. The kidney is the main organ that secretes ELA which could be released into circulation. Myocardium also has the receptor of ELA. ELA has been found to have the cardiovascular protective effect. However, whether exercise can stimulate the secretion of ELA in the kidney to exert the protective effect in the distant organ——MI heart is still a blank. This project aims to explore the effect and mechanisms of exercise-stimulated renal ELA in promoting cardiac angiogenesis and inhibiting myocardial fibrosis in MI mice. In the present research, Both in vivo animal experiments and the recombinant protein injection will be conducted to investigate the role of ELA in aerobic exercise- and resistance exercise-stimulated myocardial angiogenesis induction and fibrosis inhibition; GFP labeled adeno-associated virus vectors will be used to confirm whether exercise-stimulated renal ELA could reach the MI heart through blood circulation and play a protective role; The molecular mechanisms of ELA in exercise-improved angiogenesis and inhibited myocardial fibrosis will be explored by in vitro cell experiments. This study may provide experimental basis for the filtration of rehabilitation methods and targets of ischemic heart.