乌司他丁预处理对大鼠肝缺血再灌注多脏器氧化损伤的保护作用

目的 探讨乌司他丁预处理对大鼠肝缺血再灌注多脏器氧化损伤的保护作用机制。方法 将30只Wistar大鼠随机分为假手术(Sham-Operated,SO)组、缺血-再灌注(Ischemia-Reperfusion,I/R)组、乌司他丁(Ulinastatin,UTI)组，每组各10只。采用Pringle法制备大鼠肝I/R损伤模型。肝缺血30 min、再灌注2 h（SO组除外）,UTI组缺血前预处理UTI（3万 U/kg）。采用比色法检测血清和肝、肾、心肌组织中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cr)、尿素氮(BUN)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)、乳酸脱氢酶(LDH)水平，观察尿量和肝、肾、心肌组织病理学改变。结果 I/R组血清ALT、AST、Cr、BUN、MDA及肝、肾、心肌组织MDA含量均高于SO组(P＜0.05)，血清和肝、肾、心肌组织SOD、GSH-Px、GSH、LDH含量均低于SO组(P＜0.05)；UTI组血清ALT、AST、Cr、BUN、MDA及肝、肾、心肌组织MDA水平均低于I/R组(P＜0.05)，血清和肝、肾、心肌组织SOD、GSH-Px、GSH、LDH含量均高于I/R组(P＜0.05)。I/R组尿量少于SO组(P＜0.05)，UTI组尿量多于I/R组(P＜0.05)。组织病理学观察，I/R组肝肾组织有明显的组织损伤，心肌未见明显的组织损伤。UTI组肝肾组织结构变化明显减轻。结论 乌司他丁预处理对大鼠肝I/R后多脏器损伤具有保护作用，其机制可能与提高机体抗氧化能力有关。

Mechanism for the protective effect of ulinastain preconditioning on multiple organ injuries during hepatic ischemia-reperfusion in rats

Objective This study investigate the mechanism for the protective effect of ulinastain preconditioning on multiple organ injuries during hepatic ischemia-reperfusion. Methods The rats were randomly assigned to sham-operation (SO), ischemia/reperfusion ( I/R ) and ulinastain ( UTI ) groups with 10 rats in each group. I/R model was made by Pringle method. Group SO was the sham control. Animals in Groups I/R underwent 30 min of ischemia and 120 min of reperfusion. Rats in Group UTI underwent 30 min of ischemia and 120 min of reperfusion, preconditioning UTI (thirty thousand unit per kg) in before ischemia. Serum and multiple organ tissue levels of ALT, AST, Cr, BUN, MDA, SOD, GSH-Px, GSH, LDH and urine volume were assessed. Results The levels of serum ALT, AST, Cr, BUN, MDA, in I/R group were significantly higher than those in SO group and UTI group (P＜0.05), respectively. The serum and multiple organ tissue SOD, GSH-Px, GSH, LDH in I/R group was significantly lower than those in SO group and UTI group (P＜0.05), respectively. The urine volume in I/R group were significantly lower than that in SO group and UTI group (P＜0.05), respectively. Histological observation revealed that the obvious hepatic cell necrotic foci was surrounded by a large number of inflammatory cells infiltration in the I/R group，while the lesion was obviously alleviated in UTI group. Histological observation revealed that the obvious kidney tubules dilation in the I/R group, while the lesion was obviously alleviated in UTI group. Conclusions Ulinastatin preconditioning alleviated multiple organ injuries during hepatic ischemia/reperfusion. The mechanism may be correlated with enhancing anti-oxidation.