有氧运动诱导外泌体携带HSP22改善心肌梗死后心脏功能及其机制研究

有氧运动已被众多研究证实可以改善心肌梗死后心脏功能，但其具体机制仍然不清。我们前期研究证实热休克蛋白22（HSP22）能够通过抑制线粒体活性氧合成减轻高糖诱导的血管内皮损伤。预实验结果显示有氧运动后血浆外泌体中HSP22表达水平明显升高，并且能够抑制缺氧心肌细胞凋亡改善小鼠急性心肌梗死后心脏功能。据此，我们提出假说：有氧运动能够诱导外泌体递送HSP22至心肌细胞，通过抑制线粒体活性氧合成减轻心肌细胞凋亡与氧化应激损伤途径改善心肌梗死后心脏功能。本研究拟从分子、细胞及整体水平，利用心肌细胞缺氧模型、小鼠急性心肌梗死模型、HSP22-/-基因敲除小鼠探讨有氧运动诱导分泌的外泌体携带HSP22在防治心肌损伤方面的作用和机制。本研究或许能够为不能进行有氧运动的心肌梗死患者提供一种潜在的替代治疗方式：通过注射人工合成包含HSP22等有益分子的外泌体至心肌梗死患者体内模拟有氧运动的心肌保护作用。

Aerobic exercise is well appreciated as a protector of myocardium against myocardial infarction, but the underling mechanism remain elusive. Our previous studies evidenced that heat shock protein 22（HSP22）can reduce high glucose-induced vascular endothelial injury by inhibiting mitochondrial reactive oxygen synthesis.Furthermore,our preliminary data indicated that the expression level of HSP22 carried by exosomes in plasma was significantly increased after aerobic exercise.Moreover,we have confirmed that of plasma exosomes induced by aerobic can inhibit the apoptosis of hypoxic myocardial cells and improve cardiac function after acute myocardial infarction in mice.Based on these,we put forward the hypothesis that exosomes induced by aerobic exercise may transport HSP22 to reduce cardiomyocyte apoptosis and oxidative stress injury after myocardial infarction by inhibiting mitochondrial reactive oxygen synthesis.This study intends to probe the function and role of exosomes induced by aerobic exercise carrying HSP22 in myocardial injury at the molecular,cellular and general levels based on the myocardial cell hypoxia model,mouse acute myocardial infarction model,and HSP22-/- knockout mice.This study will verify the theory that exosomes induced by aerobic exercise are important cardioprotective factors.It also provides a potential alternative treatment for patients with myocardial infarction who cannot undergo aerobic exercise:injection of exosomes containing beneficial molecules such as HSP22 into patients with myocardial infarction to achieve simulated aerobic exercise.