谷胱甘肽合成抑制对人胚肾细胞的毒作用  

Toxic effect of inhibition of glutathione synthesis on human embryonic kidney cells

作　　者：申东晓[1] 傅娟玲[1] 史须[2] 周宗灿[1] 

机构地区：[1]北京大学医学部毒理学系 [2]北京大学人类疾病基因研究中心,北京100083

出　　处：《卫生毒理学杂志》2002年第3期150-153,共4页Journal of Health Toxicology

摘　　要：目的　研究细胞谷胱甘肽 (GSH)合成抑制对人胚肾细胞的影响。方法　用GSH合成特异抑制剂 (BSO)抑制GSH合成 ,从而降低胞内GSH的水平。测定BSO处理不同时间人胚肾细胞内GSH的水平、细胞周期的变化、活性氧水平、细胞凋亡率和细胞存活率。结果　细胞内总GSH水平随BSO处理时间的延长而下降。处理 2 4h时 ,总GSH水平下降至对照的 10 % ,分析发现细胞周期G2 M期增多 (P <0 0 1) ,S期减少 (P <0 0 5 ) ;但活性氧水平、细胞凋亡率及细胞存活率没有明显改变。处理 48h时 ,总GSH水平下降至对照的 4% ,细胞存活率明显降低 (P <0 0 1) ,活性氧水平明显升高(P <0 0 1)。细胞凋亡率直到处理 72h时升高才有显著性 (P <0 0 1,n =3 ) ,此时细胞内总GSH已基本耗竭。结论　由于GSH水平下降而引起的氧化还原状态失衡可能是凋亡发生的普遍诱导因素。Objective To investigate the effect of inhibition of GSH synthesis on human embryonic kidney cells.Methods Intracellular GSH levels was lowed by inhibiting its biosynthesis with L\|Buthionine\|(S,R)\|Sulfoximine (BSO),a specific inhibitor of γ\|glutamylcysteine synthesis.Cellular GSH cntent,ROS level,cell cycle,apoptosis and cell viability were analyzed at different times in the presence or absence of BSO.Results Total intracellular GSH level decreased about 90%,96% and 100% following BSO treatment for 24,48 and 72 h,respectively.GSH depletion didn't induce significant apoptosis until treatment with BSO for 72 h.Obvious cell cycle change was observed when treated for 24 h,cell viability decreased and ROS increased significantly after 48 h.Conclusion Redox disequilibrium induced by GSH depletion might serve as a trigger for apoptosis in human embryonic kidney cells.

关 键 词：谷胱甘肽 人胚肾细胞 细胞周期 氧化还原状态 细胞凋亡 肾毒性 

分 类 号：R99[医药卫生—毒理学]