吡咯烷二硫氨基甲酸对小鼠大剂量顺铂肾毒性损伤的防治作用  

Preventive effects of pyrrolidine dithiocarbamate on nephrotoxicity induced by high-dose cisplatin in mice

作　　者：李传刚[1] 张萌佳 舒晓宏[3] 李媛媛[3] 周琴[3] 李墨林[4] 

机构地区：[1]大连医科大学附属第二医院泌尿外科,辽宁大连116023 [2]青岛疗养院药剂科,山东青岛266071 [3]大连医科大学药物化学教研室,辽宁大连116044 [4]大连医科大学病理生理学教研室,辽宁大连116044

出　　处：《大连医科大学学报》2010年第4期388-391,共4页Journal of Dalian Medical University

基　　金：大连市科技计划项目基金资助(2009E12SF165)

摘　　要：[目的]探讨抗氧化剂吡咯烷二硫氨基甲酸(pyrrolidine dithiocarbamate,PDTC)对大剂量顺铂(cisplatin,DDP)所致肾毒性损伤的防治作用。[方法]昆明种小鼠100只,雌雄各半,依体重随机分为DDP组,DDP+PDTC组,生理盐水(NS)对照组。DDP 12 mg/kg单次腹腔内注射,PDTC 50 mg/kg每日皮下注射1次,连用3 d,等量NS对照。每组取10只小鼠,观察并记录其用药后的反应、体重变化及存活时间;分别取对照组小鼠和DDP用药后24、48、72h的DDP组和DDP+PDTC组小鼠各10只,内眦静脉取血检测肾脏功能,然后剖腹取两侧肾脏,称重并计算肾系数,统计学分析。[结果]DDP用药后24 h,DDP用药组小鼠体重下降、肾系数增高;用药后48 h,小鼠血尿素氮、肌酐含量明显升高;用药72 h 66%小鼠死亡,与对照组小鼠比较差异具有显著性意义(P<0.01)。PDTC可明显减轻DDP所致小鼠的体重下降,并能有效预防DDP用药后小鼠血尿素氮和肌酐的升高,明显提高小鼠的生存率,与DDP用药组小鼠比较差异具有显著性意义(P<0.01)。[结论]PDTC可改善小鼠DDP用药的毒副作用,预防大剂量DDP所致的肾损伤。[Objective] To observe the effects of pyrrolidine dithiocarbamate（PDTC） on nephrotoxicity induced by high-dose cisplatin（DDP） in mice.[Methods] One hundred Kunming mice,half male and half female,were randomly divided into DDP group,DDP ＋ PDTC group and control group according to body weight.Single dose of DDP（12 mg/kg） was injected intraperitoneally,PDTC（50 mg/kg） was used subcutaneously once a day for 3 days,and natural saline（NS） was given as control.Body weight and survival time of the mice in each group were measured and recorded subsequently.Blood samples were obtained from orbital venous sinus in 10 mice at 24,48,72 h after DDP administrations in every group.The levels of serum blood urea nitrogen（BUN） and creatinine（CRE） were measured by automatic analyzer and renal coefficient was calculated.[Results] Body weight of mice in DDP group decreased and renal coefficient increased significantly at 24 h after cisplatin administration.Serum BUN and CRE levels elevated significantly at 48 h after cisplatin administration and 66 % of mice died in 3d after cisplatin injection.Compared with mice treated with DDP,PDTC could obviously alleviate the degree of body weight loss,effectively prevent the elevation of serum BUN and CRE level and successfully increase the survival rate of mice after DDP administration（P0.01）.[Conclusions] PDTC could significantly reduce the side effects and prevent nephrotoxicity of the mice from high-dose DDP.

关 键 词：大剂量顺铂DDP 急性肾功能衰竭 吡咯烷二硫氨基甲酸PDTC 小鼠 

分 类 号：R965[医药卫生—药理学]