热休克预处理抑制缺血-再灌注所致心肌细胞凋亡及其机制  

Heat shock pretreatment in inhibiting myocardical apoptosis induced by ischemia-reperfusion and its mechanism

作　　者：石永忠[1] 肖卫民[1] 蒋碧梅[1] 唐道林[1] 陈广文[1] 肖献忠[1] 

机构地区：[1]中南大学湘雅医学院病理生理学教研室,长沙410078

出　　处：《中南大学学报（医学版）》2004年第5期509-512,共4页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金 (30 0 0 0 0 69;30 2 70 533) ;国家 973重点项目 (G2 0 0 0 0 5690 8);教育部博士点专项基金 (2 0 0 2 0 5330 32 )

摘　　要：目的 :探讨缺血 再灌注所致心肌细胞凋亡发生的机制及热休克预处理抑制缺血 再灌注所致心肌细胞凋亡的机制。方法 :采用结扎小鼠左冠状动脉制备在体小鼠心肌缺血 再灌注损伤 (I/R)模型 ,经DNAladder检测细胞凋亡 ,并检测caspase 3,caspase 8,caspase 9的活性。部分小鼠经热休克预处理后再进行上述实验。结果 :缺血 再灌注后心肌组织中出现DNA梯状条带 ,caspase 3,caspase 8,caspase 9活性显著增高 ;热休克预处理后 ,多种热休克蛋白 (HSPs)表达增加 ,DNA片断化减轻及caspase的活性受到抑制。结论 :缺血 再灌注损伤可激活膜死亡受体信号通路和线粒体信号通路 ,导致心肌细胞凋亡 ;通过诱导多种HSPs的表达 。Objective To explore the mechanisms of myocardial apoptosis during myocardial ischemia-reperfusion injury and to further clarify the molecular mechanisms by which heat shock pretreatment in inhibiting myocardial apoptosis induced by ischemia-reperfusion injury. Methods Myocardial ischemia-reperfusion injury was induced by the occlusion of left anterior descending branch of the coronary artery. Apoptosis was evaluated by DNA laddering assay and the activities of caspase 3,8,or 9 was measured with Caspase Colorimetric Assay Kit . Expression of heat shock proteins was detected by Western blottting analysis. To explore the effect of heat shock pretreatment on myocardium against apoptosis, mice were pretreated with whole body hyperthermia before the myocardial ischemia-reperfusion injury.Results Ischemia-reperfusion injury induced myocardial apoptosis and activation of caspase-3,8,9. Heat shock pretreatment induced the expression of several family members of heat shock proteins and inhibited myocardial apoptosis and activation of the above caspases.Conclusion Mitochondria and death receptor signaling pathways play important roles in myocardial apoptosis induced by ischemia-reperfusion injury. Heat shock pretreatment may increase the expression of several HSP, and inhibit the activation of both mitochondria and death receptor signaling pathways and apoptosis in cardiomyocytes induced by myocardial ischemia-reperfusion injury.

关 键 词：热休克预处理 心肌细胞凋亡 缺血-再灌注 抑制 CASPASE-9 HSP caspase-3 DNA片断 信号通路 表达 

分 类 号：R363[医药卫生—病理学]