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目的在庆大霉素诱导大鼠急性肾损伤模型中评价尿肾损伤分子-1(Kim-1)作为肾毒性生物标志物的诊断性能。方法 ip 60和120 mg/kg庆大霉素,每天给药1次,连续10 d,制备大鼠急性肾损伤模型。在给药第2、4、8、11天,进行肾脏组织病理分析,检测尿液Kim-1、血清尿素氮(BUN)和肌酐(Cr)水平。结果病理学结果显示,庆大霉素组大鼠出现典型肾损伤变化,呈明显的剂量及时间相关性;与对照组比较,庆大霉素低、高剂量组尿液Kim-1浓度在给药第4天即开始出现显著升高(P<0.05),增幅程度明显高于传统指标BUN和Cr,并且呈显著剂量和时间相关性;受试者操作特性曲线(ROC)结果表明,尿Kim-1的曲线下面积(AUC)明显优于BUN和Cr。结论尿Kim-1的肾毒性诊断性能优于传统肾功能评价指标,可作为一种药物肾毒性的候选生物标志物。
Objective To evaluate the diagnostic value of urinary renal injury molecule-1 (Kim-1) as a nephrotoxic biomarker in gentamicin-induced acute kidney injury model in rats. Methods 60 and 120 mg / kg gentamicin were given to the rats once a day for 10 consecutive days to prepare acute renal injury model in rats. On the 2nd, 4th, 8th and 11th day of administration, pathological analysis of renal tissue was performed to detect the level of Kim-1, BUN and Cr in urine. Results The pathological results showed that typical changes of gentamicin in rats with gentamicin showed obvious dose and time dependence. Compared with the control group, the concentrations of Kim-1 in urine of gentamicin low and high doses (P <0.05), the extent of increase was significantly higher than the traditional indicators BUN and Cr, and showed significant dose-and time-related; the results of the receiver operating characteristic curve (ROC) showed that urine Kim -1 area under the curve (AUC) was significantly better than BUN and Cr. Conclusions Urine Kim-1 is superior to traditional renal function evaluation in diagnosing nephrotoxicity and can be used as a candidate biomarker of nephrotoxicity.