线粒体通透性转换在丁烯酸内酯细胞毒性中的作用  

Role of mitochondrial permeability transition in cytotoxicity of butenolide

作　　者：王以美[1] 彭双清[1] 韩刚[1] 董延生[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2008年第2期136-139,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30340004);"十一五"国家科技支撑计划重大项目(2006BAK02A02)~~

摘　　要：目的研究线粒体通透性转换在丁烯酸内酯(BUT)细胞毒性中的作用。方法HepG2细胞染毒BUT后,采用若丹明123荧光法测定线粒体膜电位(ΔΨm)的变化;线粒体膜通透性转换孔(MPTP)抑制剂环孢素A(CsA)预处理细胞后,采用MTT法测定线粒体膜通透性转换在BUT细胞毒性中的作用。结果BUT能够浓度依赖性地降低ΔΨm,而巯基化合物谷胱甘肽、N-乙酰半胱氨酸和二硫苏糖醇则能明显抑制该效应。CsA预处理能够明显减轻BUT的细胞毒性。结论BUT通过诱导HepG2细胞内氧化应激,导致MPTP的开放而最终引起细胞死亡。AIM To study the role of mitochondrial permeability transition in the cytotoxicity of butenolide （BUT）. METHODS HepG2 cells were exposed to BUT, the mitochondrial membrane potential （△ψm） was then evaluated by the fluorescent method of rhodamine 123. HepG2 cells were pretreated with ciclosporin A （CsA）, a specific inhibitor of mitochondrial permeability transition pore （MPTP） , and the cytotoxicty was assessed by MTT assay. RESULTS Butenolide exposure resulted in the dissipation of △ψm in a concentration-dependent manner, whereas thiol-containing compounds glutathione, N-acetylcysteine and dithiothreitol pretreatment inhibited this effect significantly. CsA pretreatment provided an obvious protection against the cytotoxicity induced by BUT. CONCLUSION The cytotoxicity of BUT on HepG2 cells is mediated partially by the MPTP opening.

关 键 词：丁烯酸内酯 线粒体膜电位 线粒体通透性转换孔 细胞毒性 

分 类 号：R96[医药卫生—药理学]