蛋白酶抑制剂对肝缺血-再灌注损伤的保护作用

目的：探讨蛋白酶抑制剂及中性粒细胞在肝缺血－再灌注损伤中的作用。方法：采用大鼠部分肝缺血－再灌注模型，将健康雄性SD大鼠32只随机分为4组，手术对照组（A组），肝缺血90分钟组（B组），肝缺血90分钟，再灌注120分钟组（C组），肝缺血90分钟，再灌注120分钟加缺血前30分钟静注乌司他丁组（D组），观察动物肝组织病理切片；分别测定血浆中天冬氨酸转氨酶（AST），丙氨酸转氨酶（ALT），乳酸脱氢酶（LDH）浓度，测定肝组织中髓过氧化物酶（MPO）含量，结果：光镜下B，C2组与A组比较，肝小叶结构紊乱，肝血窦和中央静脉有程度不同的淤血，有的肝血窦变窄，内皮细胞及肝细胞普遍水肿变性；C组肝细胞坏死较B组明显；D组上述改变明显减轻，血浆中肝功能酶学指标显著升高（B，C组与A组比较，P均＜0．05），肝组织中MPO活性升高，以再灌注120分钟组为著（C组与A组比较，P＜0．01），D组血浆中ALT，AST，LDH和MPO含量均较C组明显下降，结论：肝缺血－再灌注时，聚集，黏附在肝组织中的大量中性粒细胞通过释放蛋白酶造成肝损伤，蛋白酶抑制剂乌司他丁能明显减轻这种损伤，保护肝功能。

Effect of protease inhibitor on hepatic ischemia-reperfusion 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.