The Protective Effect Of Ulinastatin Against Injury After Hepatic Ischemia And Reperfusion

The Effects of Neutrophils and Proteases Inhibitor in Hepatic Ischemia/Reperfusion (I/R) Injury in the RatObjective:To investigate the role of proteases release by neutrophils in rats after hepatic ischemia-reperfused injury. Methods:Thirty-two healthy Male SD rats were randomly divided into 4 groups(8 animals in each group). Group A animals served as sham-operated control, group B was subjected to 9 minutes lobar hepatic ischemia, group C underwent 90 minutes hepatic ischemia followed by 120 minutes reperfusion. Ulinastatin (UTI 30, OOOU/Kg) was administered to animals in group D,in which animals were reperfused 120 minutes after 90 minutes hepatic ischemia. In addition to histologic examination of liver, plasma alanine aminotransferase(ALT)aspartate aminotransferase(AST),lactate dehydrogenase(LDH) levels were respectively measured in each group. The activity of myeloperoxidase (MPO) in liver tissue wasalso determined. ResultsrHistological damage occured in 90 minutes hepatic ischemia and 90 minutes hepatic ischemia by 120 minutes reperfusion, and it was charactered by congestion in sinusoids, hepatocytic swelling or necrosis, and neutrophils infiltration. These changes were markedly alleviated in group D. Comparedto group A, plasma ALT, AST and LDH levels were significantly increased in both group B and C(all P<0.05),but they are much lower in group D than those in group C (P<0. 01). in addition, hepatic MPO activity was significantly elevated in group C, while it was markedly decreased in animals pretreated with Ulinastatin (P<0. 01).Conclusion:Neutrophil proteases appear to be involved in neutrophil accumulation and neutrophil-mediated liver I/R injury . Early treatment with Ulinastatin, a proteases inhibitor,could markedly atteneuate hepatic ischemia-reperfusion injury.