抗肿瘤坏死因子-α单克隆抗体对阻塞性黄疸大鼠肝脏保护作用的实验研究  

Experimental study about the protective effect of anti-TNF-α McAb on liver of rats with obstructive jaundice

作　　者：邱兆磊[1] 王振杰[1] 刘牧林[2] 黄建康[1] 董慧明[3] 郑士友[1] 

机构地区：[1]蚌埠医学院附属医院急诊外科,安徽蚌埠233004 [2]蚌埠医学院附属医院胃肠外科,安徽蚌埠233004 [3]蚌埠医学院附属医院肿瘤外科,安徽蚌埠233004

出　　处：《蚌埠医学院学报》2006年第3期235-237,共3页Journal of Bengbu Medical College

基　　金：安徽省教育厅自然科学研究资助项目(2002kj219)

摘　　要：目的：探讨肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）在阻塞性黄疸大鼠肝损伤中的作用及抗肿瘤坏死因子-α单克隆抗体（anti-TNF-αMcAb）的保护作用。方法：将雄性SD大鼠24只随机分为胆总管结扎组（BDL）、BDL＋anti-TNF-αMcAb组、假手术组（SO）。BDL＋anti-TNF-αMcAb组治疗于胆总管结扎后第3天开始经尾静脉注射anti-TNF-αMcAb（1mg／kg），连用5天；BDL组和SO组以同样的方法注射等量的生理盐水。分别检测各组大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和TNF-α水平，并在光镜和电镜下观察各组大鼠肝组织的病理变化。结果：BDL组及BDL＋anti-TNF-αMcAb治疗组大鼠血清ALT、AST和TNF-α水平均高于SO组（P〈0．01），但BDL＋anti-TNF-αMcAb治疗组增高的程度均低于BDL组（P〈0．05-P〈0．01），并且肝组织病理改变也较轻。SO组肝组织无明显病理改变。结论：TNF-α可能是阻塞性黄疸时肝损伤的重要介导因子，使用抗肿瘤坏死因子-α单克隆抗体，可以减轻阻塞性黄疸时肝损伤。Objective：To investigate the role of tumor necrosis factor-α（TNF-α） in liver damage in rats with obstructive jaundice and the protective effect of anti-TNF-αMcAb. Methods： Twenty-four male Sprague-Dawley rats were randomly divided into three groups ： bile duct-ligation （BDL） group, bile duct-ligation ＋ anti-TNF-αMcAb （ BDL ＋ anti-TNF-αMcAb ） group and sham-operation （SO） group. BDL ＋ anti-TNF-αMcAb group was subjected to damage with intravenous administration of anti-TNF-αMcAb（1mg/kg） for five days, starting from the 3rd day after bile duct-ligation;BDL group and SO group were administered with saline in the same manner. The levels of serum alanine amiotransferase（ ALT）, aspartate aminotransferase（AST） and TNF-α were detected in each group. The histopathology was observed by light and electron microscopy in the liver of rats with obstructive jaundice. Results：The levels of serum ALT, AST and TNF-α in BDL group and BDL ＋ anti-TNF-αMcAb group were markedly higher than those in SO group（ P 〈 0.01 ） , and the levels of serum ALT, AST and TNF-α in BDL ＋ anti-TNF-αMcAb group were much lower than those in BDL group（ P 〈 0.05 to P 〈 0.01 ）, the changes of liver histopathology were minor in BDL ＋ anti-TNF-αMcAb group. SO group had no apparent change. Conclusions：TNF-α may be one of the most important mediators in live damage induced by obstructive jaundice,and the use of anti-TNF-αMcAb can relieve the liver damage.

关 键 词：胆管阻塞 肝外 黄疸 肿瘤坏死因子-α 抗肿瘤坏死因子-Α单克隆抗体 肝损伤 大鼠 

分 类 号：R575.63[医药卫生—消化系统] R442.4[医药卫生—内科学]