目的 應用慶大霉素（GM）誘導的大鼠亞急性腎損傷模型，研究一組新的生物標志物腎損傷分子-1（kidney injury molecule-1，Kim-1）、叢生蛋白（clusterin）和胱抑素C（cystatin C）在尿液中的變化，并與傳統(tǒng)生物標志物血肌酐（SCr）和尿素氮（BUN）進行比較，評價其對腎損傷的早期預測性。方法 建立GM誘導的大鼠亞急性腎損傷動物模型，檢測不同給藥時間點模型組和對照組大鼠的SCr、BUN和尿Kim-1、clusterin與cystatin C水平，并進行腎組織病理學檢查。結果 在SCr、BUN和腎組織病理學未出現(xiàn)異常變化時，大鼠尿Kim-1、clusterin、cystatin C就表現(xiàn)出明顯的升高，并隨給藥時間延長呈線性升高。在SCr、BUN和尿Kim-1、clusterin和cystatin C測定結果的ROC曲線中，尿Kim-1、clusterin和cystatin C的曲線下面積均大于0.9。結論 尿Kim-1、clusterin和cystatin C在腎損傷中具有良好的敏感性和特異性，能夠提高對藥物誘導的腎損傷的早期預測能力。

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.

創(chuàng)新藥物研究開發(fā)技術平臺建設（2008ZX09305）