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目的研究肿瘤坏死因子-α(TNF-α)在梗阻性黄疸大鼠肾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)、胆总管结扎+抗肿瘤坏死因子-α单克隆抗体治疗组(BDL+anti-TNF-αMcAb)、假手术组(SO)。BDL组和BDL+anti-TNF-αMcAb组均作胆总管结扎复制梗阻性黄疸模型,假手术组(SO)仅麻醉、开腹而不结扎胆总管。BDL+anti-TNF-αMcAb治疗组于胆总管结扎第3天开始经尾静脉注射anti-TNF-αMcAb(1mg/kg),连用5d;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肌酐(Cr)、尿素氮(BUN)和TNF-α水平,并在光镜和电镜下观察各组大鼠肾组织的病理变化。结果 BDL组及BDL+anti-TNF-αMcAb组大鼠血清肌酐(Cr)、尿素氮(BUN)和TNF-α水平高于假手术组(SO),P<0.05。但BDL+anti-TNF-αMcAb组增高的程度低于BDL组(P<0.05),并且肾组织病理改变也较轻。SO组肾组织无明显病理改变。结论 TNF-α可能是梗阻性黄疸时肾损伤的重要介导因子,使用抗肿瘤坏死因子-α单克隆抗体,可以减轻实验鼠梗阻性黄疸时的肾损伤。
Objective To study the role of tumor necrosis factor-α (TNF-α) in renal injury in obstructive jaundice rats and the protective effect of anti-TNF-αMcAb. Methods Twenty-four male Sprague-Dawley rats were randomly divided into three groups: BDL, BDL + anti-TNF-αMcAb, . Both BDL group and BDL + anti-TNF-αMcAb group were used as model of obstructive jaundice by ligation of the common bile duct, and the sham operation group (SO) was anesthetized only without laparotomy of common bile duct. Anti-TNF-αMcAb (1mg / kg) was injected into the caudal vein on day 3 of BDL + anti-TNF-αMcAb treatment for 5 days. BDL group and SO group were injected with the same amount of normal saline . The levels of serum creatinine (Cr), blood urea nitrogen (BUN) and TNF-α were detected in each group. The pathological changes of renal tissue in each group were observed under light and electron microscopes. Results Serum creatinine (Cr), blood urea nitrogen (BUN) and TNF-α in BDL group and BDL + anti-TNF-αMcAb group were significantly higher than those in sham operation group (P <0.05). However, the increase of BDL + anti-TNF-αMcAb group was lower than that of BDL group (P <0.05), and the pathological changes of renal tissue were also lighter. There was no obvious pathological changes in SO group. Conclusion TNF-α may be an important mediator of renal injury in obstructive jaundice. The use of anti-TNF-α monoclonal antibody can reduce renal injury in experimental rat with obstructive jaundice.