脂多糖预处理对大鼠肝移植缺血再灌注期肝脏NF-κB活性和ICAM-1/LFA-1分子表达的影响  

Effects of lipopolysaccharide preconditioning on the activities of nuclear factor kappa-B and the expression of intercellular adhension molecule-1/lymphocyte function associated antigen-1 in rats graft with liver ischemia/reperfusion injury

作　　者：李洋[1] 朱继芳[1] 刘作金[1] 龚建平[1] 

机构地区：[1]重庆医科大学附属第二医院普外科,重庆400010

出　　处：《重庆医科大学学报》2009年第7期884-888,共5页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(30471696)

摘　　要：目的:探讨脂多糖(Lipopolysaccharide,LPS)预处理对大鼠肝移植缺血再灌注(Ischemia/Reperfusion,I/R)损伤中肝脏核因子-κB(Nuclearfactor-κB,NF-κB)活性和细胞间粘附分子-1/淋巴细胞功能相关抗原(Intercellular adhension molecule-1/Lymphocyte function associated antingen-1,ICAM-1/LFA-1)分子表达的影响及意义。方法:雄性SD大鼠,分为假手术组(Sham组)、原位肝移植组(OLT组)和原位肝移植+LPS预处理组(LPS组)。Sham组只开腹分离肝十二指肠韧带,OLT组和LPS组按两袖套法进行肝移植。Sham组于分离肝十二指肠韧带后0、60、180min、OLT组和LPS组于门静脉血流恢复后0、60、180min分别测定各时相点肝组织NF-κB活性、ICAM-1/LFA-1分子表达及血清ALT、AST水平。结果:再灌注后0、60、180min,OLT组与LPS组的NF-κB活性、ICAM-1/LFA-1分子表达均高于Sham组(P<0.01);再灌注后0min,OLT组与LPS组的NF-κB活性、ICAM-1/LFA-1分子表达和ALT、AST水平差异无统计学意义(P>0.05);再灌注60、180min,OLT组的NF-κB活性,ICAM-1/LFA-1分子表达,ALT、AST水平均明显高于LPS组(P<0.01)。结论:大鼠肝移植再灌注期内毒素信号转导通路的NF-κB活性增强,上调ICAM-1/LFA-1分子表达对移植肝造成损害;脂多糖预处理可有效抑制大鼠肝移植I/R中肝脏NF-κB活性、下调ICAM-1/LFA-1分子表达,对大鼠移植肝的缺血再灌注损伤有明显保护作用。Objective： To study the effects and significances of lipopolysaccharide preconditioning on the activities of NF-κB and the expression of ICAM-1/LFA-1 in rats graft liver ischemia/reperfusion injury. Methods： Male Sprague-Dawley rats were divided into three groups： sham operation group （Sham group）, orthotopic liver transplantation group （OLT group） and LPS preconditioning group （LPS group ）. Only dissecting hepatoduodenal ligament was perfomed in Sham group. Experiments of OLT were performed by two-cuff method in OLT group and LPS group. The activities of NF-κB and the expression of ICAM-1/LFA-1 in hepatic tissue ,the levels of ALT,AST in inferior caval vein blood were detected at 0,60,180 min after dissecting of hepatoduodenal ligament in Sham group and after portal vein reperfusion in OLT group and LPS group. Results： Compared with those in Sham group at the different time points respectively,the activities of NF- κ B and the expression of ICAM-1/LFA-1 were higher in OLT group and LPS group （P〈0.01）. Although the activities of NF- κB,the expression of ICAM-1/LFA-1 and the levels of ALT and AST had no significant difference between OLT group and LPS group （P〉0.05） at 0 min after reperfusion, they were evidently higher in OLT group than in LPS group （P〈0.01） at 60 min and 180 min after reperfusion. Conclusion： The activities of NF-κB were enhanced and the expression of ICAM-1/LFA-1 was upgraded in endotoxin signaling pathways during ischemia/reperfusion injury caused by liver transplantation in rat,resulting in rats graft liver ischemia/reperfusion injury. Lipopolysaccharide preconditioning can protect the rats graft liver against ischemia/reperfusion injury by significantly decreasing the activities of NF- κB and degrading the expression of ICAM-1/LFA-1.

关 键 词：肝移植 缺血再灌注损伤 脂多糖 核因子-κB 细胞间粘附分子-1 淋巴细胞功能相关抗原-1 

分 类 号：R392.11[医药卫生—免疫学] R392.12[医药卫生—基础医学]