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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

汪蓓蕾1,张瑞2,刘妍3,张金晓3,郭刚2   

  1. 1. 天津医科大学代谢病医院
    2. 天津医科大学代谢病医院内分泌研究所
    3. 天津药物研究所
  • 收稿日期:2011-04-27 修回日期:2011-09-21 出版日期:2012-02-15 发布日期:2012-02-15
  • 通讯作者: 汪蓓蕾

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

  • Received:2011-04-27 Revised:2011-09-21 Published:2012-02-15 Online:2012-02-15

摘要: 目的:观察肾损伤分子-1(kidney injury molecule-1,Kim-l)在由顺铂、庆大霉素、环孢素诱导大鼠急性肾损伤(acute kidneyinjury,AKI)模型肾组织内的变化,探讨其与AKI之间的相关性。 方法:建立庆大霉素、顺铂、环孢素诱导大鼠AKI模型,运用实时荧光定量PCR法检测肾Kim-1基因表达水平,Western blot法检测肾脏Kim-1蛋白表达水平,分析肾Kim-1表达水平与急性肾损伤的相关性。结果:病理学检查发现顺铂、庆大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。各模型组与对应对照组比较,肾Kim-l mRNA水平均高于阴性对照组,差异具有统计学意义(P 均<0.05);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。

关键词: 肾损伤分子-1, 顺铂, 庆大霉素, 环孢素, 急性肾损伤

Abstract: Objective:To study the expression of kidney injury molecule-1(Kim-1)in rat models of acute kidney injury (AKI) induced by cis-diamminedichloroplatinum (DDP), Gentamycin(GM) or cyclosporine A. Methods:3 kinds of AKI rat models were made and renal tissue was obtaind. Using those of normal rats as control, the kidney tissue was observed for histopathology.The expression of Kim-1 mRNA was detected by RT-PCR, and that of Kim-1 protein was detected by Western Blot. Results:Compared with those in control group, histopathological observation of AKI rats indicated pathological changes at various degrees, RT-PCR proved that the level of Kim-1 mRNA in renal tissue of AKI rats was up regulated, and Western blot indicated that positive expression of Kim-1 protein in renal tissue of AKI rats was progressively increseaed. Conclusion:The increase of Kim-1 in kidney tissue directly depended on the acute kidney injury induced by DDP,GM or cyclosporine A, which supported that Kim-1 can be used as a sensitive and specific biomarker for early diagnosis of acute renal tubular injury induced by chemicals.

Key words: kidney injury molecule-1(Kim-1), cis-diamminedichloroplatinum (DDP), Gentamycin(GM), cyclosporine A, acute kidney injury (AKI)