从激活ERα/PGC-1α信号通路调控线粒体融合分裂的视角探讨通脉养心方防治MI/RI作用机制

心肌缺血再灌注损伤（MI/RI）是困扰冠心病临床疗效的重要原因。线粒体融合分裂在MI/RI中起着至关重要的作用。雌激素与ERα结合激活PGC-1α，是心肌线粒体融合分裂的关键环节。中医学认为MI/RI的病理基础是正气虚损，心气不足。无阳以宣其气，无阴以养其心，MI/RI患者常伴气阴两虚症状。课题组研究发现，以“益气养阴”为治则的通脉养心方对MI/RI临床疗效显著，其可介导雌激素受体信号通路，调控心肌细胞能量代谢，但具体机制不明。本研究拟建立MI/RI大鼠模型，明确通脉养心方药效；采用液质联用整合ER报告基因技术揭示通脉养心方雌激素活性成分；应用基因沉默技术、Seahorse 线粒体功能检测等技术探讨其激活ERα/PGC-1α信号通路对线粒体的结构、功能、融合分裂蛋白及线粒体依赖性自噬的影响，揭示其抗MI/RI的作用机制，丰富“益气养阴”通脉养心方抗MI/RI的科学内涵。

Myocardial ischemia-reperfusion injury (MI/RI) is an important reason that affects the clinical efficacy of coronary heart disease. Mitochondrial fusion and division play a vital role in MI/RI. The combination action of estrogen and ERα activate PGC-1α, which is the key link in the mitochondrial fusion and division of myocardium. Based on the theory of traditional Chinese medicine, the main pathogenesis of MI/RI is due to the deficiency of positive Qi and insufficient heart Qi. There isn’t yang for proclaiming Qi and Yin for nourishing heart, so that patients with MI/RI often have symptoms of both Qi and Yin deficiency. We found that Tongmai Yangxin (TM) prescription with the treatment principle of "Yiqi Yangyin" has a significant clinical effect on MI/RI. TM can mediate the estrogen receptor signaling pathway and regulate the energy metabolism of myocardial cells, However, the specific mechanism is rarely discussed in literature. This study intends to establish the MI/RI model of rat to clarify the efficacy of TM prescription.Moreover, UPLC-QTof/MS integrated ER dual-luciferase reporter gene technology is used to reveal the estrogen active ingredients of TM prescription. With the experimental methods of RNAi technology, luminex and energy metabolism analysis technology of hippocampal XFe cells, we explore the effects of its activation of ERα / PGC-1α signaling pathway on mitochondrial structure, function, fusion cleavage protein and mitochondrial-dependent autophagy, reveal its anti-MI/RI mechanism, and enrich the scientific connotation for "Yiqi Yangyin" from TM anti-MI/RI.