肾损伤分子-1在挤压伤大鼠肾脏早期表达的研究

Protein expression of kidney injury molecule-1 in early kidney injury and clinical significance thereof： experiment with rats

目的探讨肾损伤分子-1（KIM-1）在挤压伤大鼠肾脏早期表达的情况。方法32只Wistar大鼠接受挤压单侧后肢，构建挤压伤模型，随机均分为4组，分别于解除压迫后2h．4h,6h、12h采集血液和尿液，自动生化分析检测血清肌酐（Scr）和尿肌酐urinecreatinine，UCr）。然后处死大鼠获取右肾行病理检查，并用免疫组织化学染色观察肾脏组织KIM-1蛋白的表达情况。取左肾组织，用ELISA法检测左肾组织匀浆和尿液中KIM-1蛋白的浓度。另外随机选取8只大鼠用作对照。结果各时点的scr和UCr与对照组比较均差异无统计学意义。解除压迫后6h、12h组尿液KIM-1以及肾组织匀浆KIM-1均显著高于对照组合解除压迫后2h、4h组，均P〈0．05。与未挤压组（对照组）比较，挤压伤组大鼠肾脏可见KIM-1阳性表达，且有明显时间依赖性。挤压伤组大鼠的尿液及肾组织匀浆中KIM-1的含量明显增多，且有时间依赖性。结论在挤压伤相关AKI早期，尿液中KIM-1改变的时限明显早于Scr的升高，尿KIM-1可作为AKI的早期诊断指标，其水平随着肾损伤时间的延长进行性升高，能更好地反映AKI病情的严重程度。

Objective To explore the significance of kidney injury molecule-1 （KIM-1） expression in early kidney injury caused by crush injury （CI）. Methods Thirty-two Wistar rats underwent compression upon their single hind leg for 4 h to establish CI animal models., and then randomly divided into 4 equal subgroups to undergo collection of peripheral blood and urine samples 2, 4, 6, and 12 hours after the relief of compression respectively. The urine creatinine （Ucr） and serum ereainine （Scr） were measured by automatic biochemical analyzer. After the sample collection the rats were killed and their kidney tissues were obtained to undergo pathological examination. ELISA was used to test the concentration of KIM-1 protein in urine and renal tissue homogenate. Other 8 rats without CI were used as control group. Results The Ser and Ucr values at different time point subgroups were all not significantly different from those of the control group （all P 〉 0.05）. The urine KIM-1 protein levels of the 2 h and 4 h subgroups were not significantly different from that of the control group, however, the urine KIM-1 protein levels of the 6 h and 12 h subgroups were both significantly higher than those of the 4 h subgroup and control group （all P〈 0.05）. Acute kidney injury wasa seen in the kidneys of the CI rats. The KIM-1 protein levels in the renal homogenates of the 6 h and 12 h subgroups were both significantly higher than those of the 2 h and 4 h subgroups and control group （all P〈 0.05）. The KIM-1 protein expression levels of the 4 h, 6 h, and 12 h subgroups increased time-dependently, and were all significantly higher than that of the control groupo （all P〈 0.01）.Compared with uncrushed group （control group）, the renal KIM-1 expression in crushed injury rats was visible, and had a significant time-dependent. KIM-1 levels in the extrusion of injury rats urine and kidney homogenates increased significantly in a time-dependent manner. Conclusion Appearing earlier than Scr, the change of urine KIM-1 level caan be used as a highly specific and sensitive biomarker for early diagnosis of acute tubular injury caused by CI.