过氧化氢加重铁对心肌的损伤作用及其机制

采用Langendorff灌流心脏和酶解分离的心肌细胞为实验模型,研究铁对心肌的损伤作用,以及过氧化氢对铁的心肌作用的影响及其可能机制.结果显示(1)羟基喹啉铁复合物(Fe-HQ)引起分离心肌细胞舒张期缩短,心肌细胞的收缩幅度和速度降低,离体灌流心脏左室发展压(LVDP)、±dp/dtmax、心率、冠脉流量呈现双相变化;冠脉流出液中乳酸脱氢酶(LDH)、肌酸激酶(CK)释放量和心肌丙二醛(MDA)增高.(2)H2O2可加重Fe-HQ对心脏的损伤,冠脉流出液中LDH、CK释放量和心肌MDA增高,而LVDP、±dp/dtmax和心率明显降低.(3)还原型谷胱甘肽可对抗Fe-HQ+H2O2对心肌的损伤作用,DMSO对Fe-HQ+H2O2致离体心脏损伤无明显作用.结果提示,心肌细胞内铁增加可引起心肌功能受损,H2O2可加重铁对心肌的损伤作用,其主要机制可能与@OH无关,而主要与含巯基的蛋白质受损有关.

Hydrogen peroxide augments the injury effect of iron on the isolated rat heart and cardiomyocytes

By using Langendorff perfused rat heart and enzymatically isolated cardiomyocytes, we investigated the augmented injury effect of iron on the myocardium by hydrogen peroxide and the underlying mechanisms. Cell-permeable iron (Fe-HQ) decreased the contractile amplitude, velocity and end-diastolic cell length of the cardiomyocyte but increased the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial malondialdehyde (MDA) while the left ventricular developed pressure (LVDP), +/-dp/dt(max), heart rate and coronary flow showed biphasic alterations. Hydrogen peroxide augmented the injury effect of iron accompanied by increases of coronary LDH, CK release and myocardial MDA content and decreases of LVDP, +/-dp/dt(max), and heart rate. Reduced glutathione could antagonize the injury effect of iron and hydrogen peroxide on the myocardium while dimethyl sulfoxide had no injury effect on the isolated heart. It is suggested that the functional injury of sulfhydryl group containing proteins may be involved in the augmentation of myocardial injury due to the increase of intracellular iron by hydrogen peroxide, but hydroxyl radicals may not.