抗TNF-α单克隆抗体对大鼠肝肺综合征的治疗作用

The therapeutic effects of tumor necrosis factor-α monoclonal antibody on hepatopulmonary syndrome in rats

目的：探讨抗肿瘤坏死因子-α单克隆抗体（TNF-α（mAb）对肝肺综合征（HPS）大鼠的治疗作用。方法：采用胆总管结扎（CBDL）建立大鼠HPS模型，将60只雄性SD大鼠随机分为假手术组、模型组和干预组。模型组：分别于结扎后1、2、3、4及5周麻醉动物（每个时间点6只大鼠）；干预组：于结扎后第2周，开始腹腔注射抗TNF-αmAb（0．1mg／kg·2d），干预后1、2、3及4周麻醉动物（每个时问点6只大鼠）；假手术组（6只大鼠）与5周模型组动物同批麻醉，留取各组动物的肝组织，分别行HE和Masson染色后，观察肝组织病理变化。抽取动脉血进行血气分析，计算肺泡、动脉氧分压差的变化。抽取各组动物的静脉血并分离血清，检测肝功能、内毒素、TNF-α、NO的水平。结果：干预组肝组织的炎症和纤维化明显减轻，动脉血气分析显示干预组动脉-肺泡氧分压差明显减少（P〈0．05），肝功能、内毒素、TNF-α及NO的水平较模型组明显好转（P〈0．05）。结论：抗TNF-αmAb对HPS大鼠具有治疗作用。

AIM： To investigate the therapeutic effects of tumor necrosis factor-α monoclonal antibody on hepatopulmonary syndrome in rats. METHODS： 60 adult male Sprague-Dawley rats, weighing 250 ± 25 g , were randomly divided into 3 groups： sham operation （6 rats） group, CB- DL （30 rats） group and CBDL ＋ TNF-α mAb （24 rats） group. Then CBDL operation group was divided into 5 subgroups and the CBDL ＋ TNF-α mAb group was divided into 4 subgroups. Then the rats were sacrificed and the liver tissues were removed, then HE and Masson staining was performed to observe the extent of fibrosis. The arterial blood were gotten for analysis of blood gas and observing the change of alveoloarterial oxygen difference. The change of liver function, the concentration of endotoxin, TNF-α and NO were detected. RESULTS： Compared with the CBDL group, the alveoloarterial oxygen difference decreased significantly in CBDL ＋ TNF-α mAb group. And the serum levels of ALT, TBIL decreased obviously. The concentration of ETX, TNF-α and NO in CBDL ＋ TNF-α mAb group were significantly lower than those in CBDL group. CONCLUSION： There are some therapeutic effects of tumor necrosis factor-α antibody on hepatopulmonary syndrome in rats.