PKC激活对离体心肌缺血再灌注自由基损伤和钙超载的影响

Effects of PKC activation on free radical injury and Ca2+ overload induced by ischemic-reperfusion in isolated rat heart

关键词:  缺血预处理  蛋白激酶C  自由基  钙离子  缺血/再灌注

Key words:  ischemic preconditioning, myocardium  protein kinase C  free radical  calciumion  ischemic and reperfusion

摘要:

探讨缺血预处理（IPC）保护机制中蛋白激酶C（PKC）的激活对心肌缺血再灌注后的自由基损伤和钙离子（Ca2+）代谢的影响。［方法］采用大鼠离体心脏Langendorff灌流模型，以心肌组织丙二醛（MDA）含量、线粒体中谷胱甘肽过氧化物酶（GSH-PX）活性以及线粒体Ca2+含量、细胞肌浆网钙泵（Ca2+ -ATPase）活性作为反映心肌自由基代谢及Ca2+代谢指标，观察IPC对上述指标的影响以及PKC的可能作用。［结果］与对照组比较，心肌单纯的缺血再灌注（I/R）可造成心肌明显的自由基及Ca2+代谢的异常，经过IPC可使再灌注心肌这种代谢异常明显减轻，表现为IPC组心肌组织MDA含量、线粒体Ca2+含量显著低于单纯I/R组（P均<0.01），线粒体中GSH-PX活性、肌浆网Ca2+ -ATPase活性明显高于I/R组（P<0.05）。而在预处理过程中应用多粘菌素B抑制PKC的激活，则预处理的上述有益作用可被阻断。［结论］PKC活化通过减轻心肌缺血再灌注后自由基损伤及Ca2+超载而参与心肌缺血预处理保护。

Abstract:

To investigate the effects of protein kinase C(PKC) activation in the protective mechanism of ischemic preconditioning (IPC) on free radical injury and Ca2+ metabolism after myocardial ischemic and reperfusion (I/R). ［Methods］ The Langendorff-perfused model was established in isolated rat hearts. The contents of myocardium MDA and cardiomyocyte mitochondrial Ca2+, the activities of sarcolemmal Ca2+ -ATPase and mitochondrial GSH-PX were measured as the indices of free radical and Ca2+ metabolism at the end of study. ［Results］ Compared to the control, the distinct abnormalities of free radical and Ca2+ metabolism occurred in I/R group, IPC attenuated the abnormalities induced by I/R. The contents of myocardium MDA、mitochondrial Ca2+ decreased significantly as compared to the simple I/R group(all P<0.01). The activities of mitochondrial GSH-PX and sarcolemmal Ca2+ -ATPase increased greatly compared to I/R group ( P<0.05). The PKC inhibitor Polymysin B could completely abolished the IPC protective role. ［Conclusion］ PKC activation might play an important role in IPC protection through relieving the free radical injury and Ca2+ overload against myocardial I/R injury.