化学药物诱导的大鼠急性肾损伤模型中肾损伤分子-1表达的研究  

The Study on Kim-1 Expression in Rat Model of Acute Kidney Injury Induced by Chemicals

作　　者：汪蓓蕾[1] 张瑞[1] 刘妍[2] 张金晓[2] 郭刚[1] 

机构地区：[1]天津医科大学代谢病医院,内分泌研究所,卫生部激素与发育重点实验室,300070 [2]天津药物研究所

出　　处：《天津医药》2012年第2期138-141,I0003,I0004,共6页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30571617);国家重大科技专项课题资助项目(项目编号:2008ZX09305-005)

摘　　要：目的:探讨由顺铂、庆大霉素、环孢素诱导的急性肾损伤(AKI)对大鼠肾组织内肾损伤分子-1(Kim-l)表达水平的影响。方法:将36只SD雄性大鼠随机分6组,并建立庆大霉素、顺铂、环孢素诱导大鼠AKI模型组及各对照组,每组6只。运用实时荧光定量PCR(RT-PCR)法检测肾Kim-1基因表达水平,Westernblot法检测肾脏Kim-1蛋白表达水平,分析肾Kim-1表达水平与AKI的相关性。结果:病理学检查发现顺铂、庆大霉素和环孢素对大鼠肾脏造成不同程度的肾小管损伤,所建AKI模型成功。各模型组与其对照组比较,肾Kim-lmRNA水平均升高(P<0.05或P<0.01);肾Kim-l蛋白在各阴性对照组内呈阴性结果,而在顺铂、庆大和环孢素AKI模型组内均呈阳性表达。结论:化学药物诱导AKI发生时,肾Kim-1基因转录和蛋白表达水平与肾损伤直接相关,为以尿Kim-1作为预测早期肾损伤的生物标志物提供可靠依据。Objective： To study the effect of acute kidney injury （AKI） induced by cis-diamminedichloroplatinum （DDP）, gentamycin （GM） or cyclosporine on the expression of kidney injury molecule-l（Kim-1） in rats. Methods：Thirty-six male SD rats were randomly divided into 6 groups. There were three AKI rat models established by DDP, GM and cyclospo- fine, and their three control groups respectively （n=6 for each group）. The expression level of Kim-1 mRNA was detected by RT-PCR, and the expression of Kim-1 protein was detected by Western Blot. The correlation between the expression of Kim-1 and AKI was analysed, Results：Compared with control groups, histopathological observation showed varying degrees of tubular injury in 3 kinds of AKI rat models, which indicated that models were established successfully. There were signifi- cantly higher levels of Kim-1 mRNA in model groups than those of control groups （P 〈 0.05 or P 〈0.01）. The expression of Kim-1 protein was negative in three control groups. There was a positive expression of Kim-1 protein in AKI model groups in- duced by DDP, GM and cyclosporine. Conclusion： The increase of Kim-1 in kidney tissue directly depended on the acute kidney injury induced by DDP, GM or cyclosporine, which supported that Kim-1 can be used as a sensitive and specific bio- marker for early diagnosis of acute renal tubular injury induced by chemicals.

关 键 词：膜糖蛋白类 肾疾病 顺铂 庆大霉素类 亲环素类 疾病模型 动物 聚合酶链反应 

分 类 号：R589.2[医药卫生—内分泌]