益气养阴活血中药抑制线粒体mPTP减轻缺血再灌注心肌损伤的分子机制

项目名称： 益气养阴活血中药抑制线粒体mPTP减轻缺血再灌注心肌损伤的分子机制

项目编号： No.81202779

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 李玉红

作者单位： 天津中医药大学

项目金额： 23万元

中文摘要： 冠心病是全球范围造成死亡的最主要原因，经皮冠脉介入、溶栓等心肌再灌注成为急性心梗的最有效的治疗方法，但缺血再灌注心肌损伤（MIRI）成为面临的主要难题，益气养阴活血中药（参麦注射液与丹参注射液合用）发挥中药多成分多靶点的协同作用，治疗MIRI疗效确切，但作用机制尚未见报道，本课题拟应用大鼠离体心脏、乳鼠心肌细胞，采用Western、电镜、激光共聚焦显微镜等方法，借助mPTP开放剂、PI3K及ERK1/2特异性抑制剂，研究益气养阴活血中药通过激活再灌注损伤营救激酶途径中PI3K-Akt和ERK1/2信号通路，直接抑制mPTP开放，提高线粒体的耐受性，"益气养阴以扶正"；减少活性氧产生、抑制钙超载，降低诱导mPTP开放的因素，"活血通络以祛邪"。阐明益气养阴活血中药抗MIRI的分子机制，从线粒体水平阐释中医正邪理论的科学内涵，有助于抗心肌损伤中药的研究及中医理论水平的提高。

中文关键词： 心肌缺血再灌注损伤；线粒体；心肌保护；参麦注射液；丹参注射液

英文摘要： Coronary heart disease is the leading cause of death globally. Following an acute coronary artery occlusion, timely myocardial reperfusion using either primary percutaneous coronary intervention or thrombolytic therapy remains the most effective treatment strategy. However, the full benefits of myocardial reperfusion are not realised, given that myocardial ischemia reperfusion injury will be a major clinical problem obstructing the development. Yiqi Yangyin Huoxue Chinese herb preparation （Shenmai Injection and salvia miltiorrhiza injection）have definite effect on MIRI due to multiple components and multiple targets to treat disease. The mechanisms have not been reported yet. The objective of research are to clarify that Yiqi Yangyin Huoxue Chinese herb preparation exert cardioprotective effects against MIRI in isolated perfused rat hearts and cardiomyocytes and the mechanisms involve activation of specific survival signals reperfusion injury salvage kinase (PI3K-Akt pathway and ERK1/2 pathway), hence inhibiting mitochondrial permeability transition pore opening(mPTP) directly. What is called "tonifying qi and yin to help strengthen healthy energy"； The mechanisms also involve reducing ROS generation and inhibition of calcium overload. Hence inhibiting mitochondrial permeability transition pore opening indirectl

英文关键词： Ischemia-reperfusion injury；Mitochondria；Cardioprotection；Shenmai injection；Danshen injection