Effect of protease inhibitor on hepatic ischemiareperfusion injury in rat

Objective:To investigate the role of proteases released by neutrophils in rats after hepatic ischemiareperfusion injury.Methods:Thirtytwo healthy male SD rats were randomly divided into 4 groups( 8 animals in each group).Group A animals served as shamoperated controls,group B was subjected to 90 minutes lobar hepatic ischemia, and group C underwent 90 minutes hepatic ischemia followed by 120 minutes reperfusion.Ulinastatin(UTI 30 000 U/kg) was administered to animals in group D,in which the animals were reperfused 120 minutes after 90 minutes hepatic ischemia.In addition to histological examination of the 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 was also determined.Results:Histological damage occured in 90 minutes hepatic ischemia and 90 minutes hepatic ischemia followed by 120 minutes reperfusion,and it was characterized by congestion in sinusoids,hepatocytic swelling or necrosis,and neutrophils infiltration.These changes were markedly alleviated in group D.Compared to group A,plasma ALT,AST,and LDH levels were significantly increase in both group B and C (all P 0 05), but they were 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 preatreated with Ulinastatin ( P 0 01).Conclusions:Neutrophil proteases appear to be involved in neutrophil accumulation and neutrophilmediated acute liver ischemiarepenfusion injury.Early treatment with Ulinastatin, a protease inhibitor,could markedly attenuate hepatic ischemiareperfusion injury.