目的 對(duì)腎損傷分子1（KIM-1）預(yù)測(cè)順鉑誘導(dǎo)的大鼠急性腎損傷進(jìn)行研究。方法 以順鉑為工具藥，誘導(dǎo)大鼠急性腎損傷模型。采集尿樣、腎組織樣本，對(duì)腎組織樣本進(jìn)行病理切片檢查，以確定造模是否成功。用ELISA法測(cè)定尿樣中KIM-1蛋白含量；RT-PCR法檢測(cè)大鼠腎臟KIM-1基因表達(dá)水平；Western blotting法檢測(cè)大鼠腎組織中KIM-1的蛋白含量，并通過免疫組化法定性定位分析大鼠腎組織中KIM-1蛋白表達(dá)情況，以確定急性腎損傷發(fā)生時(shí)KIM-1是否可以作為敏感的檢測(cè)指標(biāo)。結(jié)果 當(dāng)模型組大鼠腎臟皮髓交界處出現(xiàn)程度不等的腎小管擴(kuò)張，腎小管上皮細(xì)胞變性、壞死脫落，基底膜裸露等病理改變時(shí)，ELISA法檢測(cè)尿KIM-1，RT-PCR法和Western blotting法檢測(cè)腎組織中的KIM-1表達(dá)水平均明顯升高，免疫組化顯示模型組所有大鼠在腎皮髓交界部位可見大量的染色陽(yáng)性的腎小管，該染色陽(yáng)性區(qū)域與組織病理學(xué)檢查中的異常腎小管分布區(qū)域基本一致。結(jié)論 KIM-1可作為一種敏感的生物標(biāo)志物對(duì)順鉑誘導(dǎo)的大鼠急性腎損傷進(jìn)行預(yù)測(cè)。

Objective To confirm the predictive role of kidney injury molecule 1 (KIM-1) on cisplatin-induced acute kidney injury in rats. Methods Cisplatin was used to induce the acute kidney injury in rats. Urine and kidney tissues were collected, and the pathological examination of kidney tissue was used to determine if the model was successfully established. ELISA method was used to determine KIM-1 protein content in urinary, while RT-PCR, Western blotting and qualitative immunohistochemistry were taken to examine the gene expression in kidney tissues, to evaluate the expression of KIM-1, and to determine the level of KIM-1, and to analyze the expression of KIM-1 in kidney tissues, respectively, so as to confirm whether KIM-1 was a sensitive biomarker in the prediction of acute kidney injuries or not. Results The pathological changes occurred in the cortico-medullary junction of the model rats and characterized with tubular dilatation, and the epithelial cells of renal tubulars showed degeneration, necrosis, and basement membrane exposed. The expression of KIM-1 was significantly increased according to the results of ELISA, RT-PCR, and Western blotting, respectively. Meanwhile, a larger amount of positive staining of renal tubulars could be observed in the cortico-medullary junction of the kidney. The areas of the positive staining are basically the same as that of the HE staining. Conclusion KIM-1 could be used as a predictive biomarker in the cisplatin-induced acute kidney injury in rats.

國(guó)家重大新藥創(chuàng)制科技重大專項(xiàng)（2012ZX09505001-001）