目的 在慶大霉素誘導大鼠急性腎損傷模型中評價尿腎損傷分子-1(Kim-1)作為腎毒性生物標志物的診斷性能。方法 ip 60和120 mg/kg慶大霉素,每天給藥1次,連續(xù)10 d,制備大鼠急性腎損傷模型。在給藥第2、4、8、11天,進行腎臟組織病理分析,檢測尿液Kim-1、血清尿素氮(BUN)和肌酐(Cr)水平。結果 病理學結果顯示,慶大霉素組大鼠出現(xiàn)典型腎損傷變化,呈明顯的劑量及時間相關性;與對照組比較,慶大霉素低、高劑量組尿液Kim-1濃度在給藥第4天即開始出現(xiàn)顯著升高(P<0.05),增幅程度明顯高于傳統(tǒng)指標BUN和Cr,并且呈顯著劑量和時間相關性;受試者操作特性曲線(ROC)結果表明,尿Kim-1的曲線下面積(AUC)明顯優(yōu)于BUN和Cr。結論 尿Kim-1的腎毒性診斷性能優(yōu)于傳統(tǒng)腎功能評價指標,可作為一種藥物腎毒性的候選生物標志物。

Objective To evaluate the performance of Kim-1 as nephrotoxicity biomarker on rat acute kidney injury induced by gentamicin. Methods A rat model of acute kidney injury was developed by daily ip injection of 60 or 120 mg/kg gentamicin for consecutive 10 d. The histopathological analysis of kidneys was performed. The level of Kim-1 in urine, BUN and Cr in serum from different time points were determined. Results Histopathological analysis demonstrated that traditional renal injury findings were found in gentamicin-treated animals. The number of animals with tubular cell necrosis injury appeared to increase and the severity of renal damage had been aggravated over time. Urinary biomarker analysis showed that urine Kim-1 began to increase largely in animal from low- and high-dose groups since day 4, which were higher than BUN and Cr. Obvious time- and dose-response were found. ROC analysis also demonstrated that AUCs of Kim-1 was superior to BUN and Cr. Conclusion Performance of Kim-1 is better than traditional renal function markers, suggesting that it could be served as a candidate biomarker for detection of drug-induced nephrotoxicity.

十二五“關鍵技術研究”科技重大專項(2012ZX09505001-004)