目的 应用庆大霉素（GM）诱导的大鼠亚急性肾损伤模型，研究一组新的生物标志物肾损伤分子-1（kidney injury molecule-1，Kim-1）、丛生蛋白（clusterin）和胱抑素C（cystatin C）在尿液中的变化，并与传统生物标志物血肌酐（SCr）和尿素氮（BUN）进行比较，评价其对肾损伤的早期预测性。方法 建立GM诱导的大鼠亚急性肾损伤动物模型，检测不同给药时间点模型组和对照组大鼠的SCr、BUN和尿Kim-1、clusterin与cystatin C水平，并进行肾组织病理学检查。结果 在SCr、BUN和肾组织病理学未出现异常变化时，大鼠尿Kim-1、clusterin、cystatin C就表现出明显的升高，并随给药时间延长呈线性升高。在SCr、BUN和尿Kim-1、clusterin和cystatin C测定结果的ROC曲线中，尿Kim-1、clusterin和cystatin C的曲线下面积均大于0.9。结论 尿Kim-1、clusterin和cystatin C在肾损伤中具有良好的敏感性和特异性，能够提高对药物诱导的肾损伤的早期预测能力。

Objective To investigate the expression of a new panel of biomarkers, such as kidney injury molecule-1 (Kim-1), clusterin, and cystatin C, in rat model of subacute kidney injury induced by Gentamycin (GM). The evaluation of the urinary Kim-1, clusterin, and cystatin C was more sensitive and specific than that of SCr and BUN in monitoring generalized renal injury. The model of renal injury in the early prediction was established. Methods Rat model of subacute kidney injury induced by GM was established. At different time the expressions of SCr and BUN in the control and chemical-treated groups were determined, the kidney tissue was observed for histopathology, the secretion of Kim-1, clusterin, and cystatin C in urine was determined by ELISA. Results Urinary Kim-1, clusterin, and cystatin C showed a significant increase and a clear upward trend with time when serum creatinine, blood urea nitrogen, and renal histopathology do not appear abnormal level of minor changes; ELISA showed that the Kim-1, clusterin, and cystatin C contents in urine of model rats sharply increased. Comparison of the ROC areas of SCr, BUN, and urinary Kim-1, clusterin and cystatin C in the established model, and the areas of urinary Kim-1, clusterin, and cystatin C were always larger than 0.9. Conclusion Kim-1, clusterin, and cystatin C may be used as sensitive markers for early diagnosis of kidney injury induced by GM.

创新药物研究开发技术平台建设（2008ZX09305）