乌司他丁对大鼠肝脏缺血再灌注损伤后炎性反应的影响  

Ulinastatin Attenuates the Inflammatory Reaction Induced by Hepatic Ischemia Reperfusion in Rats

作　　者：陈伟新[1] 杨立群[2] 

机构地区：[1]复旦大学附属中山医院青浦分院普外科,上海201700 [2]第二军医大学附属东方肝胆医院ICU,上海200433

出　　处：《中国临床医学》2012年第3期259-261,共3页Chinese Journal of Clinical Medicine

摘　　要：目的:探讨乌司他丁(ulinastatin,UTI)预处理对大鼠肝脏缺血再灌注(ischemia reperfusion,IR)损伤后炎性反应的影响,并研究高迁移率蛋白B1(high mobility group box 1,HMGB1)在UTI预处理机制中的作用。方法:采用SD大鼠70%肝脏IR损伤模型,即在肝脏缺血45min后再灌注2h。将40只大鼠随机为4组,分别为0.9%氯化钠对照组(对照组,n=10)、UTI预处理组(UTI组,n=10)、UTI+HMGB1拮抗剂组(UTI+Anti-HMGB1组,n=10)和乌司他丁+HMGB1诱导剂组(UTI+rHMGB1组,n=10)。比较各组大鼠在IR后血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)的水平;采用酶联免疫吸附试验检测各组大鼠血清中肿瘤坏死因子α(tumornecrosis factor-alpha,TNFα)和白细胞介素1(interleukin 1,IL1)的水平;对各组大鼠的肝组织进行HE染色观察其病理学改变;采用免疫组织化学染色方法检测各组大鼠肝组织中HMGB1蛋白的表达水平。结果:与对照组相比,UTI组在IR后血清中ALT、AST均显著降低(P<0.05)。UTI+rHMGB1组IR后血清TNFα、IL1水平与对照组相比无显著差异(P>0.05);UTI组和UTI+Anti-HMGB1组IR后血清TNFα、IL1水平与对照组相比均显著降低(P<0.05)。肝组织病理显示,UTI组和UTI+Anti-HMGB1组的肝细胞坏死和中性粒细胞浸润显著轻于对照组和UTI+rHMGB1组。免疫组织化学染色显示,UTI组和UTI+Anti-HMGB1组肝细胞HMGB1表达程度显著低于对照组(P<0.05)。结论:UTI预处理可以显著抑制大鼠肝IR损伤后肝细胞中HMGB1的表达水平以及下游炎症因子的水平,从而减轻IR损伤;HMGB1诱导剂可逆转UTI的肝保护作用。Objective：To investigate the effect of pretreatment with Ulinastatin（UTI） on the inflammatory reaction induced by hepatic ischemia reperfusion（IR） in rats and the role of high mobility group box 1 （HMGB1） . Methods：SD rat models of he- patic IR （45 minutes of partial ischemia and 2 hours of reperfusion） were used in this study. Forty rats were randomly divided into four groups： 0. 90//00 saline group（control group）,UTI group,UTI ＋ anti-HMGB1 group and UTI ＋ rHMGB1 group. Blood and hepatic tissue samples have been harvested after reperfusion. Serum alanine aminotransferase（ALT） and aspartate aminotransferase（AST） have been detected. Serum levels of tumor necrosis factor-a（TNFa） and interleukin-1 （ILl） have also been detected. HE staining have been done to observe the pathological changes of the liver tissues in each group . The expres- sion of HMGB1 in hepatic tissues was assessed by immunohistochemical staining. Results： Serum levels of ALT,AST, TNFa and ILl in UTI group and UTI ＋ anti-HMGB1 group were significantly lower than those in control group and UTI ＋ rHMGB1 group （P〈0.05）. There was no significant difference in the serum levels of TNFa and ILl between control group and UTI ＋ rHMGB1 group （P〉0.05）. Hepatic structures were better maintained and apoptotic hepatic cells were less in UTI group and UTI ＋ anti-HMGB1 group, compared with control group and UTI ＋ rHMGB1 group（P^0.05） . Levels of HMGB1 in UTI group and UTI ＋ anti-HMGB1 groups were significantly lower than those in control group（P〈0.05）. Conclusion： Pretreat- ment with UTI can reduce the expression of HMGB1 and thus attenuate liver injury through its anti-inflammatory effects. The effects of UTI can be turned over by rHMGB1.

关 键 词：乌司他丁 肝脏 缺血再灌注 高迁移率蛋白B1 

分 类 号：R961[医药卫生—药理学]