线粒体在丁烯酸内酯致细胞氧化损伤中的作用  

Role of mitochondria in cellular oxidative injuries induced by butenolide

作　　者：王以美[1] 彭双清[1] 周琦[2] 王敏伟[2] 韩刚[1] 闫长会[1] 阳海鹰[1] 王国强[1] 

机构地区：[1]军事医学科学院毒物药物研究所 [2]沈阳药科大学药学院药理学系,辽宁沈阳110016

出　　处：《中国药理学与毒理学杂志》2006年第6期484-489,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30340004)~~

摘　　要：目的研究线粒体呼吸链是否是丁烯酸内酯(But)致细胞内活性氧过量产生的来源,及其在But致细胞毒性中的作用。方法线粒体呼吸链复合物特异性抑制剂及线粒体氧化磷酸化解偶联剂预处理HepG2细胞后,染毒But。采用MTT法测定细胞存活率,二氯荧光素荧光法测定细胞内活性氧的产生。结果呼吸链复合物Ⅰ,Ⅱ,Ⅲ和Ⅳ抑制剂鱼藤酮、噻吩甲酰三氟丙酮(TTFA)、抗霉素A、氰化钾及氧化磷酸化解偶联剂羰氰氯苯腙(CCCP)能够明显改变But所致细胞内活性氧的产生。鱼藤酮和抗霉素A能够增强But引起的细胞毒性,而CCCP则能明显减轻But引起的细胞毒性。结论线粒体呼吸链是But致细胞内活性氧过量产生的重要来源,且活性氧的过量产生在But的细胞毒性中发挥着重要的作用。AIM Butenolide （But） is a myco- toxin produced by Fusarium species. Previous studies showed that But induced overproduction of intracellular reactive oxygen species （ROS） , and had significant effects on the activities of mitochondrial respiratory chain complexes. Whether the mitochondrial respiratory chain is the source of ROS induced by But was studied, and its role in the cytotoxicity of But was also studied. METHODS HepG2 cells were pretreated with specific inhibitors of mitochondrial respiratory chain complexes and a mitochondrial oxidative phosphorylation uncoupler, then exposed to But. Cell viability was determined by MTT assay, and intracellular ROS production was evaluated by dichlorofluorescein fluorescence. RESULTS Specific inhibitors of respiratory chain complexes Ⅰ , Ⅱ , Ⅲ and Ⅳ of rotenone, thenoyltrifluoroacetone （ TTFA ） ,antimycin A and potassium cyanide, and the mitochondrial uncoupler carbonyl cyanide mchlorophenylhydrazone （CCCP） resulted in obvious changes of intracellular ROS production. Rotenone and antimycin A significantly aggravated the cytotoxicity induced by But, whereas CCCP markedly alleviated the cytotoxicity induced by But. CONCLUSION Mitochondrial respiratory chain is the important source of ROS overproduction induced by But, and the ROS play an important role in the cytotoxicity induced by But.

关 键 词：丁烯酸内酯 细胞 HepG2 线粒体 鱼藤酮 毒性 

分 类 号：R114[医药卫生—卫生毒理学]