洛铂和顺铂对血管内皮细胞及肝、肾细胞损伤的体外实验研究

Damage effects of lobaplatin and cisplatin on endothelia,liver and kidney cells in vitro

目的分析洛铂(LBP)和顺铂(DDP)对传代培养的人脐静脉内皮细胞株(HUVECs)、人肝细胞株(QSG-7701)和人近端肾小管上皮细胞(HK-2细胞)的抑制作用,并初步探讨其可能机制。方法采用MTT法检测LBP和DDP对HUVECs、QSG-7701和HK-2细胞抑制作用的差异,并测定HK-2细胞培养液中丙二醛(MDA)和超氧化物歧化酶(SOD)含量,观察LBP和DDP对HK-2细胞脂质过氧化过程的影响。结果在相同浓度、相同作用时间下,DDP组对HK-2细胞抑制率明显高于LBP组(P<0.05),而LBP组对HUVECs细胞的抑制率明显高于DDP组(P<0.05);LBP组和DDP组对QSG-7701抑制率的差异无统计学意义(P>0.05);此外,与空白对照组比较,LBP组和DDP组均使HK-2细胞培养液中MDA含量明显升高,SOD活性明显降低(P均<0.05),但LBP组和DDP组间差异无统计学意义(P>0.05)。结论 LBP和DDP均对肝、肾细胞有较强的抑制作用,LBP的肾细胞毒性较DDP低,LBP组对正常人脐静脉内皮细胞抑制作用明显强于DDP组,提示LBP可能具有更强的抑制血管形成的能力;氧化性损伤可能是两者造成肾毒性的机制。

Objective To study the damage effect of lobaplatin（LBP） and cisplatin（DDP） on human umbilical vein endothelia cell line（HUVECs）,human liver cell line（QSG-7701） and human renal tubular epithelial cells（HK-2 cells）,and to explore the possible mechanism.Methods The proliferation responses of HUVECs,QSG-7701 and HK-2 cells treated with LBP or DDP in the concentration of 3.125ug/ml were observed by MTT assay.In addition,the concentrations of malondialdehyde（MDA） and superoxide dismutase（SOD） were determined in HK-2 cells.Results With the same concentration and action time,the inhibition effect of DDP on HK-2 cells was significantly higher than that of LBP（P〈0.05）,while the inhibition effect of LBP on HUVECs was significantly higher that that of DDP（P〈0.05）.The inhibition rate of these two drugs on QSG-7701 was not significantly different（P〉0.05）.The level of MDA in LBP-treated group or DDP-treated group was significantly higher than that in control group（P〈0.05）,the level of SOD in both platinum groups was significantly lower than that in control group（P〈0.05）,while both the levels of MAD and SOD were not significantly different between LBP-treated group and DDP-treated group（both P〉0.05）.Conclusion LBP and DDP displayed inhibitive effect on human hepatocytes and renal tubular epithelial cells.LBP might have stronger anti-angiogenesis effect on HUVECs comparing to DDP.Oxidative damage may be a common mechanism of renal toxicity caused by LBP and DDP.