血红素氧化酶-1在异氟烷预处理肝脏保护机制中的作用  

Role of heme oxygenase-1 in protective effect of Isoflurane preconditioning against rat hepatic ischemia-reperfusion injury

作　　者：陈国忠[1] 吕欣[2] 叶林杰[1] 杨立群[2] 陈伟新[2] 俞卫锋[2] 

机构地区：[1]南京军区福州总医院麻醉科,350025 [2]第二军医大学东方肝胆外科医院麻醉科

出　　处：《上海医学》2010年第12期1096-1099,共4页Shanghai Medical Journal

基　　金：南京军区重点项目资助(07Z039)

摘　　要：目的研究血红素氧化酶(HO)-1的表达及活性的改变对肝脏缺血再灌注损伤的影响,及其在异氟烷预处理肝脏保护中的作用。方法将40只雄性Sprague-Dawley大鼠随机均分为5组:假手术(Sham)组;肝脏缺血再灌注对照组(I/R组),肝脏缺血60 min,再灌注4 h;异氟烷预处理-肝脏缺血再灌注(I/R-ISO)组,1.4%异氟烷吸入预处理30 min后再行缺血再灌注处理;肝脏缺血再灌注组-异氟烷预处理HO-1抑制剂(Iso-Znpp)组,于缺血再灌注前1 h先于腹腔内注射锌原卟啉(ZnPP),其余处理同I/R-ISO组;肝脏缺血再灌注HO-1诱导剂(I/R-hemin)组,缺血再灌注前24 h于腹腔内注射HO-1诱导剂血红素(hemin),其余处理同I/R组。观察各组大鼠肝组织的病理改变,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肝脏髓过氧化物酶(MPO)活性,以及肝组织及血清肿瘤坏死因子(TNF)-α的表达等情况。采用免疫组织化学方法测定HO-1的表达。结果与I/R组比较,I/R-ISO和I/R-hemin组的ALT、AST水平均显著降低(P值均<0.05);与I/R-ISO组比较,Iso-Znpp组ALT、AST均显著升高(P值均<0.05)。与Sham组比较,I/R、I/R-ISO、Iso-Znpp、I/R-hemin组血清及肝组织中TNF-αmRNA水平均显著升高(P值均<0.05);与I/R组比较,I/R ISO和I/R-hemin组血清及肝组织中TNF-αmRMA水平均显著降低(P值均<0.05);与I/R-ISO组比较,Iso-Znpp组血清及肝组织中TNF-α水平均显著升高(P值均<0.05)。与Sham组比较,I/R、I/R-ISO、Iso-Znpp、I/R-hemin组肝脏MPO活性均显著升高(P值均<0.01);与I/R-ISO组比较,Iso-Znpp组肝脏MPO活性显著升高(P<0.05)。Sham组几乎无HO-1表达,I/R组可见HO-1少量表达,I/R-ISO、ISO-Znpp、I/R-hemin组HO-1表达均显著高于I/R组。结论 HO-1的诱导表达可明显减轻肝脏缺血再灌注损伤和相应的炎性反应,异氟烷预处理可明显上调肝脏缺血再灌注损伤后HO-1的表达,HO-1活性抑制剂ZnPP可反转异氟烷预处理的肝脏保护及抗炎作用,提示异氟烷预�Objective To investigate HO-1 expression and its activity on the hepatic l/R injury,and its role in the protective effect of isoflurane pretreatment against hepatic l/R injury in rats.Methods A total of 40 male SD rats was randomly assigned to 5 group（n = 8）：Sham group;l/R group,receiving 60 min of hepatic ischemia and 4h of reperfusion;l/R-lso group,receiving 1.4%isoflurane for 30min before IR;IR-lso-HO-1 inhibitor group（Iso-Znpp group）,receiving Znpp（25μmol/kg,IP） 1 h before isoflurane and IR;and l/R-HO-1 inducer group（l/R-Hemin）,receiving hemin,an HO-1 inducer,24 h before IR.A model of segmental hepatic ischemia was used,and the serum ALT,AST levels,hepatic myeloperoxidase activity and TNF alpha mRNA in the liver and serum were assessed.Immunoreactivity of HO-1 was performed in the liver tissue after hepatic l/R.Results Compared with l/R group,l/R-ISO and l/R-Hemin had significantly lower levels of ALT and AST（all P0.05）. Compared with l/R-ISO,Iso-Znpp group had significantly higher levels of ALT and AST（P0.05）.Compared with Sham control group,the rest four groups had significantly higher levels of TNF-αin the serum and hepatic tissue （P0.05）;compared with l/R group,l/R-ISO and l/R-Hemin groups had significantly lower levels of NF-α（all P0.05）;compared with l/R-ISO group,Iso-Znpp group had significantly lower levels of NF-α（all P0.05）. Compared with the sham group,the rest 4 groups had significantly higher MPO activity in hepatic tissues（all P 0.01）;compared with l/R-ISO group,Iso-Znpp had significantly higher level of MPO（both P0.05）.There were hardly any expression of HO-1 in the Sham control group;slight HO-1 expression was found in l/R group,and strong expression was found in the rest groups.Conclusions Expression of HO-1 can greatly attenuate hepatic l/R injury and the related inflammation.Clinical relative dosage of isoflurane pretreatment for 30 min might increase the HO-1 expression after hepatic ischemia-reperfusion and attenuate liver IR injury.

关 键 词：肝脏缺血再灌注 异氟醚 预处理 血红素氧化酶-1 

分 类 号：R614[医药卫生—麻醉学]