线粒体介导的热应激心肌细胞凋亡分子机制的研究

建立热应激心肌细胞实验模型，揭示热应激心肌细胞线粒体生物学变化与细胞凋亡发生的相关性，观察线粒体结构与功能的改变对Cyt C释放及其活化Caspase-9启动的酶解级联反应的影响；研究Bcl-2对此凋亡的通路的阻抑作用，确认线粒体在热致心肌细胞凋亡中的介导作用，探讨热应激心肌细胞凋亡的分子机制和调控环节，为热应激机体心功能紊乱的防治提供新思路。

The present study was designed to investigate the mechanism underlying myocardium injury induced by heat stress. The results showed that the mitochondrial structure and function in cardiomyocytes were destructed under heat stress, which in turn lead to severe disorders of intracellular homeostasis including Ca2+ overload and oxidative stress. Exposing to these special internal environmental states, cardiomyocyte apoptosis was occurred. Mitochondrial permeability transition (MPT) pore opening played an important role in stress-induced cardiomyocyte apoptosis, which resulted from Bcl-2 and Bax, protein locating on mitochondrial membrane, expression change and followed by Cytochrome C release from mitochondria. The latter activated caspase-3 and subsequent apoptosis. Bcl-2 possessed certain protective effect on the heat stressed cardiomyocytes, which was realized by protecting mitochondria and inhibiting the process from the release of Cytochrome C to the activation of Caspase cascade. These finding implied the pathway from heat stress via mitochondria to cardiomyocyte injury. Fas-mediated cardiomyocyte apoptosis represented an other important mechanism involved in cardiomyocyte injury induced by heat stress.