有氧运动裨益心血管健康，但具体机制不明。我们新近发现4周游泳运动大鼠循环外泌体具有显著的心脏保护作用；进一步通过miRNA测序及功能验证，在运动外泌体中筛选出12个差异表达miRNAs，其中miR-342-5p对缺氧/复氧心肌细胞具有显著保护作用，提示有氧运动通过循环外泌体miRNA介导的心脏保护新机制，且miR-342-5p可能是一种新的心脏保护“运动因子”。本课题拟在上述发现基础上，①阐明miR-342-5p保护缺血心脏的主要作用机制，尤其是其对心肌线粒体功能的影响及其分子机制；②明确有氧运动致循环外泌体miR-342-5p升高的组织/器官来源；③明确运动员是否也存在循环外泌体miR-342-5p增高；④初步探讨化学修饰的外泌体或miR-342-5p用于心脏保护的可能性。本研究可望揭示有氧运动心脏保护的一个新机制及一个新的运动因子，为运动健身提供新的理论依据并为心脏保护提供新思路。

Aerobic exercise not only reduces cardiovascular risk factors but also confers direct endogenous cardiovascular protection. However, the mechanisms underlying the cardioprotective effects of exercise are still unclear. Our recent study has shown that exercise-derived circulating exosomes afford significant cardiovascular benefits after 4-week swimming training in rats. Through miRNA profiling assay and qRT-PCR analysis, 12 differentially expressed miRNAs have been identified in exercise-derived circulating exosomes, among which miR-342-5p stood out as the most potent cardioprotective molecule. The findings suggest a novel endogenous cardioprotective mechanism that aerobic exercise-derived circulating exosomal miRNAs protect the ischemic heart, with exosomal miR-342-5p as a potential cardioprotective exerkine. The specific aims of this proposal include: 1) To further decipher the role of miR-342-5p in exercise-afforded cardioprotection, especially in the regulation of myocardial mitochondrial homeostasis; 2) To identify the tissues/organs that produce and release exosomal miR-342-5p after long-term aerobic exercises; 3) To determine whether exosomal miR-342-5p is elevated in humans after exercise training; 4) To explore the potential therapeutic interventions of modified exosomes enriched with miR-342-5p. Elucidation of novel cardioprotective exerkines and their mechanism of actions for long-term aerobic exercise-afforded cardioprotection will offer new therapeutic strategies and targets for ischemic heart diseases.