心肌缺血再灌注损伤(MIRI)是影响心肌梗死病人预后的关键因素。线粒体相关内质网膜(MAM)广泛参与Ca2+转运和磷脂代谢, 影响线粒体功能, 调控细胞凋亡。MAM水平异常增加与MIRI密切相关。但MAM形成和解离的动态过程及其调控还亟待阐释。VDAC1/GRP75/IP3R1构成Ca2+从内质网至线粒体的高效通道。环氧二十碳三烯酸(EETs)具有显著抗MIRI作用。我们前期发现EETs抑制内质网应激和MAM形成，改善线粒体功能；分子对接显示EETs能与VDAC1、GRP75、IP3R1相互作用，提出假说：EETs通过VDAC1/GRP75/IP3R1下调MAM水平抗MIRI。本课题考察EETs对VDAC1/GRP75/IP3R1复合物的影响，观察其它MAM构成蛋白PACS-2、Mfn2、MCU、SERCA、Sig1R等的变化，提高对MAM动态及其调控的认识，为综合防治MIRI提供新思路。

Myocardial ischemia reperfusion injury (MIRI) is the key factor influencing the prognosis of patients with myocardial infarction. Mitochondria associated endoplasmic reticulum (MAM) is widely involved in the metabolism of phospholipids, calcium signaling, and cell apoptosis. Increase MAM levels were closely associated to MIRI. But the dynamic process under MAM formation and dissociation and its regulation also needs to be elucidated. VDAC1/GRP75/IP3R1 constitutes Ca2+ efficient pathway from the endoplasmic reticulum to mitochondria. As metabolic products of arachidonic acid, epoxyeicosatrienoic acids (EETs) can effectively protect against MIRI. Our previous studies suggested that EETs can supress endoplasmic reticulum stress and MAM level, improve mitochondrialin function. Molecular docking demonstrates EETs can interact with VDAC1, GRP75, IP3R1, the hypothesis that EETs depresses MAM level through VDAC1/GRP75/IP3R1 to protect against MIRI. This project intends to investigate the effects of EETs on VDAC1/GRP75/IP3R1 complex, and changes in MAM constituents PACS-2, Mfn2, MCU, SERCA, Sig1R, etc. This study will provide the knowledge about MAM and prpose a novel therapeutic choice in MIRI.