心肌缺血性病变是导致猝死的重要原因，转录因子HIF2A调节缺血引起的心肌组织细胞缺氧适应并影响心肌损伤程度、心功能、心室重构等，但机制有待阐明。形态学分析难以认定早期局灶性心肌缺血缺氧损伤，我们前期研究发现多种人体解剖组织中缺氧适应相关因子的表达定量随着损伤失血后的生存时间延长而变化，提示这些因子的定量检测对缺血缺氧性组织损伤评价具有应用价值。本课题采用细胞学实验、HIF2A敲除小鼠心梗模型以及人体解剖心肌组织来系统研究心肌缺血性病变中HIF2A调节缺氧适应的分子机制，阐明HIF2A在保护心肌、改善心功能、心室重构在心梗后心衰方面的作用机制，为临床诊断和治疗提供潜在靶点。并且在法医解剖人体心肌组织中加以验证，定点采样、定量检测HIF2A及其下游相关因子，拟对心肌缺血责任动脉认定提供有利生物学证据，以期弥补仅依赖病理形态学分析的不足，为心肌缺血导致的心源性猝死的病理学鉴定提供新的客观依据。

Myocardial ischemia is an important cause of sudden death. Transcription factor HIF2A regulates hypoxic adaptation of myocardial cells induced by ischemia and affects myocardial injury, cardiac function and ventricular remodeling, but the mechanism remains to be elucidated. Morphological analysis is difficult to identify early focal myocardial ischemia and hypoxia injury. Previous studies have found that the expression of hypoxic adaptation-related factors in various human tissues changes with the prolongation of survival time after injury and hemorrhage, suggesting that quantitative detection of these factors has practical value in the evaluation of ischemic and hypoxic tissue injury. The molecular mechanism of HIF2A regulating hypoxic adaptation in myocardial ischemic lesions will be systematically studied by cytological experiments, myocardial infarction model of HIF2A knockout mice and human myocardial tissue. The mechanism of HIF2A protecting myocardium, improving cardiac function and ventricular remodeling in post-myocardial infarction heart failure will be elucidated to provide potential targets for clinical diagnosis and treatment. It will also be verified by forensic human myocardial tissue, by fixed-point sampling and quantitative testing of HIF2A and its downstream related factors, in order to provide favorable biological evidence for the identification of responsible artery for myocardial ischemia, to make up for the deficiency of relying only on pathological morphological analysis, and to provide a new objective basis for the pathological identification of sudden cardiac death caused by myocardial ischemia.