【摘要】 目的研究人源化抗人肿瘤坏死因子-α单克隆抗体（recombinant humanization anti-human tumor necrosis factorαmonoclonal antibody,rhTNF-McAb）对人TNF-α转基因小鼠自发性关节炎的治疗作用。方法以市售药物Adalimumab为阳性药物,通过给予不同剂量的rhTNF-McAb对转基因小鼠的自发性足肿胀度、小鼠四肢综合肌力和踝关节组织病理学变化,用ELISA法检测小鼠体内人TNF-α质量浓度、血药质量浓度和抗药物抗体质量浓度。结果rhTNF-McAb(0.5 mg·kg^-1,1.5 mg·kg^-1,4.5 mg·kg^-1)腹腔给药对人TNF-α转基因小鼠的自发性足肿胀有显著的治疗作用,并呈现明显的剂量依赖性关系,作用机制与阳性药物Adalimumab一致。但rhTNF-McAb在小鼠体内的清除情况,产生抗药物抗体的滴度与Adalimumab明显不同。结论rhTNF-McAb可以显著的抑制人TNF-α,并且其疗效更优于已上市类似药物Adalimumab。更多还原

【Abstract】 Objective To study the protective effect of humanized anti-human TNF-α monoclonal antibody（ rhTNF-McAb） on spontaneous arthritis of human TNF-α transgene mouse. Methods After injecting the positive drug adalimumab and different doses of rhTNF-McAb,the idiopathic paw swelling,muscular strength and ankle joint histopathology of transgene mouse were observed. ELISA assays were performed to determine human TNF-α concentration,blood drug concentration and anti-drug antibodies concentration.Results The intraperitoneal injection（ i. p.） of rhTNF-McAb( 0. 5 mg·kg^-1,1. 5 mg·kg^-1,4. 5 mg·kg^-1)significantly and dose-dependently inhibited idiopathic paw swelling in human TNF-α transgene mouse,and the action mechanism of rhTNF-McAb was same with that of adalimumab. However, the drug clearance,antidrug antibodies concentration of rhTNF-McAb were different from that of adalimumab. Conclusions The results suggest that rhTNF-McAb significantly inhibited human TNF-α and the therapeutic effect of rhTNFMcAb was better than that of adalimumab.更多还原