多种药物联合应用对小鼠顺铂肾毒性的拮抗作用  

Combined effects of agents against nephrotoxicity induced by cisplatin in mice

作　　者：廖英俊[1] 金亚平[2] 汤浩[1] 

机构地区：[1]中国医科大学基础医学院生理学教研室,辽宁沈阳110001 [2]中国医科大学公共卫生学院劳动卫生与职业病学教研室,辽宁沈阳110001

出　　处：《中国药理学与毒理学杂志》2009年第3期219-224,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30571590)~~

摘　　要：目的探讨硫酸锌(Zn)、亚硒酸钠(Se)、磷霉素钠(Fos)、乙酰半胱氨酸(NAC)、硫代硫酸钠(STS)、蛋氨酸(Met)和牛磺酸(Tau)等对顺铂肾毒性的联合拮抗作用。方法采用7因素(7个药物)2水平(给药或不给药)的正交设计,共8个实验组。各组小鼠ig给予不同组合的拮抗药物,每日1次,连续9d。从第3天起,ig给予拮抗药后6h,ip顺铂3.5mg.kg-1,连续5d,分别于给予顺铂前和实验结束前测量小鼠体重。给药结束次日,摘小鼠眼球取血,然后处死。快速取肾组织,并分别测定血清尿素氮(BUN)、肾还原型谷胱甘肽(GSH)含量及谷胱甘肽过氧化物酶(GSH-Px)活性。结果Zn,Fos和Met可显著改善顺铂引起的体重减轻;Fos和Met可显著降低顺铂引起的肾脏系数升高;Fos,STS和Met可显著抑制顺铂引起的血清BUN和肾GSH含量升高;Met可显著抑制顺铂引起的肾GSH-Px活性升高。单独给予Se,NAC和Tau对以上指标未见明显改善作用。结论多种药物联合应用可协同拮抗顺铂的肾毒性作用,以Zn(或Se),Fos(或STS)和Met联合应用的拮抗效果最好。AIM To explore the protective effects of zinc sulfate （Zn） , sodium selenium （ Se ）, fosfomycin （ Fos ）, N-acetyl-cysteine （ NAC ）, sodium thiosulfate （ STS ）, methio- nine （Met） and taurine （Tau） on nephrotoxicity induced by cisplatin. METHODS Animal experiment was carried out based on the orthog- onal design, and mice were divided into 8 groups according to the orthogonal table of Ls （27） setting 7 factors with 2 different levels. Mice were supplemented by gavage with various combinations of agents as designed in the or- thogonal table once a day for nine days. Three days later, 3.5 mg. kg -1 of cisplatin was given intraperitoneally once a day for 5 d simultane- ously, and rat weights were measured before cisplatin was given and before experiment fin- ished. Twenty-four hours after cessation of sup- plementation, blood was taken by removing the eyes, and kidneys were taken rapidly after sac- rificing mice. Contents of blood urea nitrogen （BUN） in serum and reduced glutathione （GSH） in kidney and activities of glutathione peroxidase（GSH-Px） in kidney were analyzed.RESULTS Zn, Fos and Met could ameliorate obviously the cisplatin-induced weight loss; Fos and Met could ameliorate obviously the cispla- tin-induced increase in kidney ratio; Fos, STS and Met could ameliorate obviously the eispla- tin-induced increase in BUN levels in serum and GSH levels in kidney; Met could ameliorate obviously the eisplatin induced increase in GSH-Px activities in kidney. How- ever, supplementation of Se, NAC or Tau alone failed to show any beneficial effects. CON- CLUSION The potentiated effects for preven- tion of cisplatin induced nephrotoxicity could be achieved via combined use of the agents. The optimal combination of agents for prevention of cisplatin induced nephrotoxicity was Zn （or Se） , Fos （ or STS） and Met.

关 键 词：顺铂 肾/毒性 药物拮抗作用 蛋氨酸 磷霉素 硫酸锌 亚硒酸钠 硫代硫酸钠 

分 类 号：R969.2[医药卫生—药理学] R994.1[医药卫生—药学]