谷胱甘肽对顺铂致大鼠肾小管上皮细胞毒性的影响

Effects of glutathione on toxicity of primary cultured rat renal tubular epithelial cells induced by cisplatin

目的 探讨顺铂对不同年龄大鼠肾小管上皮细胞的毒性及谷胱甘肽 (GSH )对其影响。方法 从不同年龄的雄性大鼠分离的肾小管上皮细胞接种于 96孔培养板 ,培养 2 4h后加入一系列浓度的顺铂 ,或在加入顺铂前 16和 4h ,分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸 ,再培养 2 4h后用MTT方法检测细胞存活率。结果 顺铂对5、2月龄和 3周龄大鼠肾小管上皮细胞半数抑制浓度 (IC50 )分别为 2 43 42、178 16和 15 9 0 6μmol L ;BSO能使 3组IC50 分别降低到 1 62、1 3 0和 1 47μmol L ,而半胱氨酸则可使 3组IC50 均大于 5 0 0 0 μmol L。 结论 顺铂对不同年龄大鼠肾小管上皮细胞均具有明显的毒性 ,BSO和半胱氨酸可分别增强和减弱顺铂的毒性 ,间接证明细胞内GSH对顺铂所致大鼠肾小管上皮细胞毒性有保护作用。

Objective To investigate the effects of glutathione(GSH) on cisplatin-induced toxicity to renal tubular epithelial cells(RTEC)isolated from different age rats.Methods RTEC were isolated from 3-week-old,2-month-old or 5-month-old rats and inoculated into 96 well plates,after 24 hours' preincubation,a series of concentrations of cisplatin,in the presence and absence of L-cysteine or DL-buthionine-(S,R)-sulfoximine(BSO),were added,and after 24 hours' coincubation,MTT assays were performed to test cell viability.Results The concentrations of cisplatin that inhibited 50% cell growth(IC_ 50 ) of RTEC from 5-month-old,2-month-old or 3-week old rats were 243\^42,178\^16 and 159\^06 μmol/L,respectively,BSO made IC_ 50 of cisplatin lower down to 1\^62,1\^30 and 1\^47 μmol/L,respectively,while L-cysteine made IC_ 50 of Cisplatin increase up to more than 5 000 μmol/L. Conclusion Cisplatin is dramatically toxic to RTEC from different age rats;BSO can enhance Cisplatin-induced cytotoxicity,while L-cysteine can protect it,it is indirectly proved that GSH can protect cisplatin-induced toxicity to RTEC from rats.