蛋白激酶CaMKⅡ激活是心肌缺血再灌注(I/R)诱导细胞凋亡及程序性坏死的中心环节。动物冬眠时CaMKII活性降低。我们自主合成的冬眠诱导剂3-碘甲状腺胺（T1AM）抑制I/R诱导细胞死亡，但机制不明。推测外源性T1AM唤醒机体潜在的冬眠机制，抑制细胞凋亡及程序性坏死，减轻心肌I/R损伤。为此，我们构建心肌I/R损伤模型、上/下调T1AM受体TAAR1表达以及CaMKII的活性，在整体、离体心脏、细胞水平研究T1AM及低温对I/R损伤诱导心肌细胞凋亡与程序性坏死的作用异同，从CaMKII相关的细胞内钙离子调控、线粒体PTP开放方面研究T1AM抑制细胞死亡的调控机制。本研究可望明确恒温动物是否存在类似冬眠保护心肌机制，拓展对心肌死亡特别是程序性坏死调控的认识，为寻求减轻I/R损伤的新治疗策略提供思路，为开发T1AM相关药物提供实验证据。

CaMKII activation plays a nodal role in apoptosis and necroptosis induced by myocardial ischemia reperfusion (I/R). The activity of CaMKⅡis reduced during animal hibernation. A hibernation inducing agent 3-iodothyronamine (T1AM), synthesized autonomously by our team, has been found to inhibit myocardial I/R-induced apoptosis and necroptosis, but its mechanism remains to be elucidated. To address the issue, we will carry out serial experiments to construct myocardial I/R injury model and to up/down-regulate T1AM receptor TAAR1 expression and CaMKII activity. The differences and similarities between T1AM and low temperature affecting I/R-induced myocardial apoptosis and necroptosis will be examined in vivo, ex vivo and in vitro. The underlying mechanism by which T1AM inhibits I/R-induced myocardial cell death will be investigated, as to the CaMKⅡ-related intracellular calcium handling and opening of mitochondria permeability transition pore（PTP）. The findings of this study should elucidate if hibernation mechanism of myocardial protection exists in warm blooded animal, provide a novel therapeutic strategy to reduce the damage of I/R, deepen the understanding of myocardial necrosis death, especially necroptosis, and add the experimental evidence for the development of T1AM and related drugs for myocardial protection.