谷胱甘肽对顺铂所致肾小管上皮细胞毒性的保护作用

Protective effects of glutathione on cisplatin-induced toxicity to primary cultured rat renal tubular epithelial cells without sex-dependent difference

关键词:  顺铂  肾小管上皮细胞  性别  谷胱甘肽(GSH)  BSO  半胱氨酸

Key words:  Cisplatin  renal tubular epithelial cells  sex  glutathione  DL-buthionine-(S,R)-sulfoximine（BSO）  L-cysteine

摘要:

探讨谷胱甘肽(GSH)对顺铂所致不同性别大鼠肾小管上皮细胞毒性的影响。［方法］ 从不同性别的大鼠分离的肾小管上皮细胞接种于96孔培养板，培养24h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合成前体物半胱氨酸，再培养24h后用MTT方法检测细胞存活率。［结果］ 顺铂对雌雄大鼠肾 小管上皮细胞具有形状相似的剂量-反应关系曲线，半数抑制浓度（IC50）分别为0.178 mmol/L和0.182 mmol/L；BSO能使2组IC50均降低为0.001mmol/L，可使剂量-反应曲线左移，而半胱氨酸则可使2组IC50均升高，均大于5 mmol/L，使剂量-反应曲线下沉。［结论］ 顺铂对雌雄大鼠肾小管上皮细胞同样具有明显的毒性；BSO和半胱氨酸可分别增强和降低顺铂的毒性，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，且与性别无关。

Abstract:

To investigate the protective effects of glutathione (GSH) on cisplatin-induced toxicity to renal tubular epithelial cells isolated from different sex rats. ［Methods］ Renal tubular epithelial cells were isolated from different sex rats and inoculated into 96-well culture plates, after 24 hours' preincubation, a series of concentration of cisplatin, in the presence and absence of DL-buthionine-(S,R)-sulfoximine(BSO), inhibitor of GSH synthesis, or L-cysteine, precursor of GSH synthesis, were added, and after 24 hours' coincubation, MTT assay was performed to test cell viability. ［Results］ The concentrations of cisplatin that inhibited 50% cell growth(IC50) of renal tubular epithelial cells from female or male rats were 0.182 mmol/L and 0.178 mmol/L, respectively, and they had similar dose-response curves; BSO made both of IC50 of cisplatin lower down to 0.001　mmol/L, while L-cysteine made both of IC50 of cisplatin increase up to more than 5 mmol/L. ［Conclusion］ Cisplatin is dramatically toxic to renal tubular epithelial cells from female or male rats; BSO can enhance cisplatin-induced cytotoxicity, while L-cysteine can protect cisplatin-induced cytotoxicity, it is indirectly proved that GSH can protect cisplatin-induced toxicity to renal tubular epithelial cells from rats without sex-dependent difference.