Boelsterli Urs A, Hsiao Chin-Ju J
University of Connecticut, School of Pharmacy, Department of Pharmaceutical Sciences, Storrs, CT 06269-3092, United States.
Drug Discov Today. 2008 Nov;13(21-22):982-8. doi: 10.1016/j.drudis.2008.08.002. Epub 2008 Sep 11.
Mitochondria have been increasingly implicated in being a crucial subcellular target and amplifying oxidative injury induced by many drugs. Among the major cytoprotective antioxidants is the mitochondrial matrix protein, superoxide dismutase-2 (SOD2). Genetic modification of the expression of SOD2 by transgenic techniques or gene silencing has generated a number of distinct animal models with SOD2 deficiency including the heterozygous Sod2(+/-) knockout mouse model. These mice display a discreet underlying mitochondrial stress but are otherwise phenotypically normal and thus model a variety of clinically silent mitochondrial abnormalities. The model has found application in oxidative stress and age-related research, but it is only recently that it has been successfully used to study mechanisms of idiosyncratic drug-induced liver injury.
线粒体越来越多地被认为是一个关键的亚细胞靶点，并且会放大许多药物诱导的氧化损伤。线粒体基质蛋白超氧化物歧化酶2（SOD2）是主要的细胞保护性抗氧化剂之一。通过转基因技术或基因沉默对SOD2的表达进行基因改造，已经产生了许多不同的SOD2缺陷动物模型，包括杂合子Sod2(+/-)基因敲除小鼠模型。这些小鼠表现出轻微的潜在线粒体应激，但在其他方面表型正常，因此可模拟各种临床上无症状的线粒体异常。该模型已应用于氧化应激和衰老相关研究，但直到最近才成功用于研究特异质性药物性肝损伤的机制。
