心肌缺血再灌注损伤（MIRI）是阻碍心血管疾病治疗及预后的难题。mTOR通路在MIRI中发挥重要保护作用。课题组发现多功能Tudor-SN蛋白是mTOR通路的新靶分子，在心肌细胞分化成熟中发挥调控作用。基于前期工作基础，我们提出假设，mTOR/Tudor-SN/YAP在MIRI中发挥心肌保护作用。MIRI中mTOR通路激活后上调Tudor-SN，随后Tudor-SN调控YAP促进心肌修复，并通过抗凋亡及氧化应激的作用抵抗损伤，保护心肌。本课题将利用Tudor-SN转基因、敲除及野生型小鼠构建MIRI模型：1.明确MIRI下mTOR通路激活对Tudor-SN表达调控作用。2.探索Tudor-SN调控YAP入核，促进心肌细胞增殖及再生，发挥心脏保护作用机制。3.从基因转录调控水平探讨Tudor-SN蛋白调控心肌氧化应激和凋亡的机制。本研究将为深入探讨临床MIRI的治疗及预防提供理论基础。

Myocardial ischemia reperfusion injury (MIRI) is a major obstacle in treatment and prognosis of cardiovascular diseases. mTOR signaling pathway plays an important protective role in MIRI. Recently, we demonstrated that multifunctional Tudor-SN protein , as a new target molecule of mTOR signaling pathway, involves in the regulation of development and maturation of cardiac myocytes. Based on previous work, we hypothesize that mTOR/Tudor-SN/YAP signaling pathway may participate in myocardial protection under MIRI. The possible mechanisms are as follows: mTOR pathway is activated under MIRI, and then upregulates the expression of Tudor-SN. Tudor-SN then promotes myocardial reparation through inducing YAP nuclear location. Meanwhile, Tudor-SN may protect the myocardium through regulating apoptosis and oxidative stress. In this project, we will investigate the underlying molecular mechanisms of Tudor-SN in cardiac protection under MIRI. Tudor-SN-KO, TG and WT C57BL/6N mices will be utilized to build the MIRI model. We'll detect the activity of mTOR pathway and the expression of Tudor-SN under MIRI. Then, we'll explore the mechanism of Tudor-SN promotes myocardial cell proliferation and regeneration under MIRI through regulating the location of YAP protein. Meanwhile we'll detect the influence of Tudor-SN on oxidative stress, stress granules formation and apoptosis in mice MIRI model and H9c2 cell lines, and reveal the underlying mechanism through transcriptional regulation. This study will provide new therapeutic targets and strategies to the clinical treatment and prevention of MIRI .