钙敏感受体与缺血/再灌注损伤诱发心肌细胞凋亡的线粒体途径的关系

目的探讨钙敏感受体（CaR）参与心肌缺血／再灌注损伤诱发细胞凋亡的机制。方法Langendorff离体灌流的方法复制心脏缺血／再灌注模型。观察缺血／再灌注和加入CaR激动剂时CaR的表达情况。TUNEL染色观察不同组别细胞凋亡,应用激光扫描共聚焦显微镜观察大鼠心肌细胞的线粒体膜电位的变化。Western blot检测心肌组织线粒体中细胞色素C及Bcl-2的表达。结果心肌缺血／再灌注和加入CaR激动剂时CaR的表达明显高于对照组（P均〈0．01）。TUNEL染色发现缺血／再灌注组和激动剂组细胞凋亡率明显增加（P均〈0．05）,同时此两组的线粒体膜电位下降明显（P均〈0．05）,线粒体细胞色素C与Bcl-2的表达也明显下降（P均〈0．05）。结论CaR激活在缺血／再灌注时通过诱发线粒体损伤,促进细胞凋亡。

The role of calcium-sensing receptor on ischemia/reperfusion-induced rat cardiomyocyte apoptosis

OBJECTIVE: To investigate the role of calcium-sensing receptor (CaR) on ischemia/reperfusion-induced rat cardiomyocyte apoptosis. METHODS: The isolated rat hearts were subjected to 40 min ischemia followed by 2h of reperfusion with or without CaR agonist GdCl3 at the beginning of reperfusion. Control hearts (without ischemia) and ischemic hearts (40 min ischemia without reperfusion) served as controls. The protein expressions of CaR, Bcl-2 and cyt C were detected by Western blot. Cardiomyocyte apoptosis was detected by TUNEL. Mitochondrial potential (Deltaphim) was detected by laser confocal microscopy. RESULTS: Compared to controls groups, the expressions of CaR and apoptotic cells were significantly increased, Deltaphim and expressions of mitochondria cyt C and Bcl-2 were significantly reduced in ischemia/reperfusion hearts with or without GdCl3. CONCLUSION: CaR was involved in the induction of cardiomyocyte apoptosis during ischemia/reperfusion via mitochondrial pathway.