Calcineurin在大鼠心脏缺血预处理中的作用  

The Role of Calcineurin in Ischemia Preconditioning of Rat Heart

作　　者：李淑莲[1] 齐永芬[2] 陈亚红[2] 张英[2] 王晓红[2] 唐朝枢[2] 

机构地区：[1]开封医学专科学校病理生理学教研室,河南省开封市475001 [2]北京医科大学第一医院心血管研究所,北京市100034

出　　处：《中国动脉硬化杂志》2000年第2期103-106,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目!(39730220)

摘　　要：为观察环孢霉素 (syclosporinA)对缺血预处理心脏保护作用的影响 ,探讨Calcineurin信号通路在心脏缺血预处理中的作用 ,制备离体大鼠心肌缺血 再灌注模型 ,测定心功能和心肌Calcineurin活性。结果发现 ,缺血预处理明显减轻缺血 再灌注的心功能抑制 ,与单纯缺血 再灌注比较 ,冠状动脉灌流量、收缩期左室内压最大变化速率和舒张期左室内压最大变化速率分别减少 39% (P <0 .0 5 )、33 % (P <0 .0 1)和 5 2 % (P <0 .0 5 ) ,心肌钙含量下降2 1% (P <0 .0 1)。Calcineurin抑制剂环孢霉素A可抵消缺血预处理的心肌保护作用。此外 ,缺血 45min 再灌 15min使心肌Calcineurin活性升高 ,与对照组相比较 ,Calcineurin活性增加 1.9倍 (P <0 .0 1)。单纯缺血预处理组心肌Cal cineurin的活性较对照组增加 2 .3倍 (P <0 .0 1)。环孢霉素A预先处理心脏则完全阻断了缺血预处理诱导的Calci neurin激活 ,与缺血预处理组相比较 ,其活性下降 75 % (P <0 .0 1)。Aim To observe the effect of cyclosporin A( a inhibitor of calcineurin). On cardioprotection induced by ischemia preconditioning (IPC) and explore the role of calcineurin (CaN) signal pathway in IPC. Methods The model of ischemia /reperfusion (I/R) was produced in isolated rat heart. The cardic functions and the activity of myocardium calcineurin were mersured. Results It was found that IPC apparently attenuated the inhibition of cardic function induced by I/R. Compared with I/R group, in IPC group coronary perfusion flow(CPF),+LVdp/dt max and -LVdp/dt max decreased by 39%(P<0.01),33%(P<0.01) and 52%(P<0.01) respectively. Myocardial calcium content decreased by 21%(P<0.01). However CsA, the inhibitor of CaN, can conteract the cardioprotection effect of IPC. In addition, the activity of cardiac calcineurin was activated by cardiac I/R, compared with control group, the activity of CaN increased by 1.9 folds; ischemia preconditoning alone activated the activity of cardiac calcineurin and increased by 2.3 folds (P<0.01) compared with control group. Before ischemia preconditioning administration of CsA completely blocked the activation of calcineurin stimulated by IPC. Compared with IPC group, its activity decreased by 75%(P<0.01). Conclusion The results suggest that IPC-induced cardioprotective efffects are mediated by calcineurin pathway.

关 键 词：CALCINEURIN 环孢霉素A 再灌注损伤 心脏缺血 

分 类 号：R541.4[医药卫生—心血管疾病]