过氧化氢加重铁对心肌的损伤作用及其机制  

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

作　　者：陈莹莹[1] 沈岳良[1] 曹春梅[1] 徐万红[1] 钱忠明[2] 夏强[1] 

机构地区：[1]浙江大学医学院生理教研室,杭州310006 [2]香港理工大学应用生物与化学技术系

出　　处：《生理学报》2001年第3期175-182,共8页Acta Physiologica Sinica

基　　金：Thus work was supported by the Natural Science Foundation of Zhejiang for the Outstanding Young Scientists (No. RC9803).

摘　　要：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；冠脉流出液中乳砰脱氢酶（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 Ｆｓ－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。By using Langendorff perfused rat heart and enzymatically isolated cardiomyocytes, we investi-gated the augmented injury effect of iron on the myocardium by hydrogen peroxide and the underlying mecha-nisms. 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/dtmax, 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/dtmax, and beast 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 sulfh ydryl group containing proteins may he involved in the augmentation of myocardial injury due to the increase of intracellular iron by hydrogen peroxide, but hydroxyl radicals may not.

关 键 词：铁 心脏 过氧化氢 心肌损伤 

分 类 号：R363[医药卫生—病理学]