糖尿病小鼠线粒体氧化磷酸化功能与自由基的关系  

OXIDATIVE PHOSPHORYLATION FUNCTION OF LIVER CELL MITOCHONDRIA IN MICE AND ITS RELATIONSHIP WITH FREE RADICAL IN DIABETES

作　　者：张蕾[1] 陈顺志[1] 刘树森[2] 

机构地区：[1]辽宁省锦州医学院,锦州121000 [2]中国科学院动物研究所生物膜与膜生物国家重点实验室

出　　处：《现代预防医学》2008年第7期1348-1350,1352,共4页Modern Preventive Medicine

摘　　要：[目的]用四氧嘧啶(Alloxan)建立实验性糖尿病小鼠模型,探讨糖尿病状态下线粒体氧化磷酸化功能改变的机理和自由基的关系。[方法]分别从整体、组织和线粒体水平测定抗氧化酶活性,线粒体水平测定:①以琥珀酸(S)为底物的呼吸控制:态3呼吸速率(R3)、态4呼吸速率(R4)、呼吸控制比(RCR)和磷氧比(P/O);②H+-ATPase合成活力;③测定O·2-的生成量。[结果]糖尿病小鼠ATP合酶活性显著降低45.99%;O2·-含量增加35.8%;线粒体呼吸链RCR、P/O显著降低(P﹤0.01),State4显著增高(P﹤0.01);血清和肝组织、线粒体SOD活性,GSH含量显著降低(P﹤0.001)。[结论]证明实验性糖尿病小鼠肝功能损伤是氧化性损伤,氧化应激又是该损伤的结果,其原因以电子漏增加为主,导致质子漏增加,自由基生成量增多,ATP合酶活性下降,无效耗氧增加、线粒体受损。[Objective] Experimental animal diabetic model built by Alloxan were used to investigate the mechanism of changes of mitochondrial oxidative phosphorylation during the diabetes and its relationship with free radical. [ Methods ] Determined activity of antioxidant enzyme respectively in blood, liver tissue, and liver mitochondria, and determined parameter of mitoehondria respiratory： （1） respiratory control with Succinate （S） as substrate： respiratory rate of state 4 （Rate 4）, respiratory rate of state 3 （Rate 3）, respiratory control rate （RCR） and P/O; （2） H^＋-ATPase synthesis activity; （3） contents of super oxide anion O2·^-. [Results] In diabetic mice, H^＋-ATPase Synthesis activity decreased by 45.99%; the mitochondrial O2·^- of liver increased by 35.8%; there was a significant decrease in RCR and P/O with both substrates （P 〈 0. 01 ）. Rate 4 increased significantly （P 〈 0. 01 ）. The significant decrease of SOD activity and GSH contents were observed among the blood, liver tissue and liver mitoehondria （P〈 0. 01）. [Conclusion] Liver function damage of diabetic mice is the oxidative damage, and oxidative irritability is the result of the oxidative damage. The enhanced mitochondrial electron leak induces the proton leak and the content of free radical increase, H^＋-ATPase synthesis activity decrease and the ineffective consumption of oxygen increase.All of these may be mainly responsible for the function damage of mitochondrial during diabetes.

关 键 词：线粒体 呼吸链 呼吸活性 超氧阴离子 糖尿病 

分 类 号：R587.1[医药卫生—内分泌] R774.5[医药卫生—内科学]