Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: The role of Bcl-2 family proteins and ERK1/2
Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: The role of Bcl-2 family proteins and ERK1/2
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DOI：
10.1007/s10495-006-0292-5
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发表时间：
2006-12-01
期刊：
影响因子：
7.2
通讯作者：
Kremastinos, D. T.
中科院分区：
文献类型：
--
作者：
Lazou, Antigone;Iliodromitis, E. K.;Kremastinos, D. T.
目的：缺血预处理（IPC）可抑制缺血再灌注后心肌细胞凋亡。本研究的目的首先是检查是否短期机械拉伸与急性压力超负荷（MPC），这已被证明可以减少缺血/再灌注后的梗死面积，模仿IPC在减弱心肌细胞凋亡和第二，以评估是否诱导心脏保护涉及Bcl-2家族蛋白的表达和磷酸化的促生存激酶的调制。方法与结果：采用麻醉家兔模型，预处理方案包括一个周期的短暂缺血/再灌注，或短期机械牵拉急性压力超负荷。预处理刺激同样有效地减少梗死面积，再灌注4小时后确定。IPC可减轻心肌细胞凋亡，而MPC无此作用。IPC可恢复缺血再灌注心脏Bcl-2和Bcl-xL表达的下降。Bax水平各组间无差异。IPC组和MPC组再灌注时ERK 1/2均被激活。结论：缺血再灌注后，细胞凋亡和坏死对梗死面积的影响是独立的。IPC对心肌细胞凋亡过程的抑制可能涉及抗凋亡蛋白Bcl-2和Bcl-xL表达的调节。ERK 1/2可能参与细胞凋亡和坏死的抑制。
Objective: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases. Methods and Results: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or shortmechanical stretch with acute pressure overload. Preconditioning stimuli were equally effective in reducing the infarct size, determined after 4 h reperfusion. However, IPC but not MPC attenuated myocardial apoptosis. IPC restored the decreased expression of Bcl-2 and Bcl-xL observed in hearts subjected to ischemia and reperfusion only. Bax levels were not different among the groups. ERK1/2 were activated during reperfusion in both IPC and MPC groups. Conclusions: The data provide further evidence that apoptosis and necrosis contribute independently to infarct size after ischemia and reperfusion. Inhibition of the myocardial apoptotic processes by IPC may involve modulation of the expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL. ERK1/2 may be involved in the inhibition of both apoptosis and necrosis.