克山病心肌线粒体膜氧化损伤的实验研究及其发病学意义

经过多年研究证明克山病是一种以心肌线粒体膜损害为主要特征的地方性心肌病,这次通过用克山病区低硒粮模拟病区居民生活喂养幼豚鼠15周,结果发现血及心、肝等组织,线粒体、微粒体及上清中的硒水平及谷胱甘肽过氧化物酶活性下降,谷胱甘肽转硫酶活性未见升高,甚而降低。脂质过氧化物、氢过氧化物及荧光色脂增加,线粒体膜脂中的心磷脂减少,同时线粒体内膜结合酶的细胞色素氧化酶(CCO)活性下降,即出现了膜的氧化损伤和膜功能障碍。在向提纯的 CCO 中加心磷脂的重组复性试验中实现了 CCO 活性的明显增加,可见线粒体膜结构与功能的异常是克山病患者心肌能量代谢障碍乃至心肌坏死等病理改变的基础。

Experimental study of oxidative damage in mitochondrial membrane of myocardium of keshan disease and its pathogenetic significance

Keshan disease (KD) is an endemic cardiomyopathy with membrane damage inmyocardial mitochondria.We have obtained a result through feeding guinea pIgs adiet collected from KD endemic area with imitation of the living comditionsof inhabitants in the area.Selenium (Se) contet and glutathione peroxidase acti-vity in blood and tissues was decreaseb in mitochondria,microsome and superna-tant of myocardium.The activity of glutathone-s-transferase was also decreasedto some extent,Therefore,the content of lipid peroxide and hydroperoxide increa-sed.Meantime the activity of cytochrome oxidase (CCO),an enzyme binding withmitochondrial membrane,and the cardiolipin in membrane lipids decreased.There fure oxidative damage in the membrane and disorders of the membrane function appe-ared.Added the cardiolipin to purified CCO solution in the reconstruction test,CCO activity increased significantly.Hence the abnormalities of structure,confor-mation and function of the mitochondrial membrane might be the source of themetabolic disorder of the energy and/or the occurrence of necrosis in myocardiumof te Patients with Keshan disease.