天津医药

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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

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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)