抗TNF-α抗体治疗大鼠肝肺综合征  

The treatment of hepatopulmonary syndrome using anti-tumor necrosis factor-α monoclonal antibody in rats

作　　者：冯英梅[1,2] 刘丽[1] 刘楠[1] 赵芝[1] 

机构地区：[1]河北医科大学第二医院消化内科河北省消化病重点实验室河北省消化病研究所,河北石家庄050000 [2]辛集市第一医院,河北辛集052360

出　　处：《基础医学与临床》2012年第1期61-65,共5页Basic and Clinical Medicine

基　　金：河北省医学科学研究重点课题(08080)

摘　　要：目的探讨抗TNF-α单克隆抗体(TNF-αMcAb)对肝肺综合征(HPS)大鼠NF-κB表达的影响及NF-κB在抗TNF-α单克隆抗体治疗大鼠肝肺综合征中的作用。方法用胆总管结扎术(CBDL)建立大鼠HPS模型,经腹腔注射抗TNF-αMcAb(0.1 mg/kg.2 d)治疗HPS,HE染色观察肺组织病理变化;放射免疫法检测血浆TNF-α的水平;鲎试剂盒检测血浆内毒素水平;进行血气分析,计算肺泡-动脉氧分压梯度差的变化;Western blot方法进行肺组织NF-κB蛋白表达定量分析。结果抗TNF-αMcAb干预后肺组织的炎性反应和毛细血管扩张明显减轻;肺泡-动脉氧分压梯度差明显减少(P<0.05);血浆内毒素和TNF-α的水平较胆总管结扎组明显减低(P<0.05);肺组织NF-κB蛋白表达水平显著下降(治疗前:0.93±0.23;治疗后:0.75±0.18)(P<0.05)。结论抗TNF-α单克隆抗体可能通过抑制NF-κB的表达治疗肝肺综合征。Objective To study the effects of anti-tumor necrosis factor-α monoclonal antibody on the expression of NF-KB on hepatopulmonary syndrome in rats and the effects of NF-kB in treating hepatopulmonary syndrome in rats with anti-tumor necrosis factor-α monoclonal antibody. Methods The experimental models of HPS in rats were developed with eommom bile duct ligation, and then were injected with anti-TNF-αMcAb （0. 1 mg/kg 2 d）intraperitoneally, Lung histopathologieal changes were evaluated by hematoxylin and eosin staining; TNF-α concentration in plasma was measured by radioimmunity method; The endotoxin in the plasma was checked by tachypleus amebocyte lysate kit; Hepatopulmonary syndrome was assessed by measurements of alveoloarterial oxygen difference （ P（A-a） O2 ）. Western blot was employed to investigate the expression and the changes of NF-KB in hepatopulmo- nary rat lungs. Results Compared with the CBDL group, there was a gentle vasodilatation and widen interalveolar septum in lung in anti-TNF-αMcAb treament group, the level of the P （A-a）02 was significantly lower （P 〈 0. 05 ）.The concentration of ETX and TNF-α were significantly lower（ P 〈 O. 05 ）. The expression of NF-KB in CBDL ＋ anti-TNF-α McAb group（0. 75 ±0. 18） decreased obviously than those in CBDL group（0.93 ± O. 23 ） （ P 〈 O. 05 ）. Conclusions Anti-tumor necrosis factor-or antibody can reduce the expression of NF-kB and attenuate the severity of hepatopulmonary syndrome through downregulateing the expressiion of NF-kB.

关 键 词：肿瘤坏死因子-α 肿瘤坏死因子-α单克隆抗体 肝肺综合征 核转录因子-ΚB 

分 类 号：R575[医药卫生—消化系统] R563[医药卫生—内科学]