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Acta Pharmacol Sin. 2004 Oct;25(10):1334-40.

Effects of ulinastatin on renal ischemia-reperfusion injury in rats.

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Department of Anesthesiology, Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009,China.



To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats.


Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12,500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope.


Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significant effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion.


The protease inhibitor, ulinastatin, reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

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