葡甲胺对染铂大鼠肾损害的预防及机理初探

Preventive Effect of Meglumine on Rat's Nephrotoxicity Induced by Cisplatin and Discussion on its Mechanism

目的 观察葡甲胺 (NMG)预处理对染铂 (CP)大鼠肾损害相关指标的影响 ,初步探讨其预防机理。方法 以3个剂量NMG预处理后给予CP ,收集染毒后 12～ 2 4h、6 0～ 72h、10 8～ 12 0h尿液 ,分别于染毒后 3、5天处死动物留取血液及肾脏 ,测定相关指标 ,行抗小鼠体内S180 肉瘤试验 ,称瘤重 ,计算瘤重抑制率。结果 NMG预处理明显降低CP所致大鼠肾脏系数升高 ,抑制血尿素氮 (BUN)、肾皮质丙二醛 (MDA)含量升高 ,降低肾皮质铂含量 ,且随NMG剂量升高 ,作用越显著。染铂大鼠排铂高峰由染铂后 10 8～ 12 0h提前至 6 0～ 72h ,且随NMG剂量升高 ,排铂高峰越明显。NMG预处理对CP抗S180 活性无影响。结论 NMG预处理明显预防染铂大鼠肾损害且不影响CP抗肿瘤活性。其可能机理是NMG预处理促使染铂大鼠排铂高峰提前 ,促进尿铂排泄。

Objective To study the effect of Meglumine(NMG) on several correlated parameters in rats exposed by cisplatin(CP),and preliminarily approach its possible mechanism.Methods The rats of experimental groups were exposed by CP after the NMG-pretreatment.All rats were killed on 3th or 5th days after treatment.Using different ways to measure the changes of several correlated parameters.The effect of NMG on the antitumor activity of CP was measured in mice bearing S\-\{180\}.Results The ratio of kidney weight to body weight,the level of blood urea nitrogen (BUN),malondialdehyde (MDA) in kidney cortex,and platinum concentration in kidney cortex of experimental groups all lower than those of the CP group rats.The climax of excretion of urinary platinum was advanced to 60-72h from 108-120h.With increase in dose of NMG,the effect of mentioned above was more outstanding.And NMG-pretreatment didn't influence the antitumor activity of CP.Conclusion NMG may prevent renal injury induced by CP and not influence the antitumor activity of CP.To advance the climax of the excretion of urinary platinum and promote the elimination of urinary platinum may be one of the mechanisms.