重组人肿瘤坏死因子受体融合蛋白抗类风湿性关节炎机制研究

Experimental Study on Action Mechanism of RhTNFR:Fc Therapy in Rheumatoid Arthritis in Rats

目的:探讨重组人肿瘤坏死因子受体融合蛋白(rhTNFR:Fc)对胶原诱导的Wistar大鼠类风湿性关节炎(CIA)动物模型的滑膜细胞凋亡影响。方法:模型随机分为阴性对照组、阳性对照组和rhTNFR:Fc组。rhTNFR:Fc组按17.5μg·kg(-1)每d皮下注射(ih)1次;阴性对照组ih等量0.9%氯化钠溶液;阳性对照组每d ih甲氨蝶呤(MTX),31 d后抽取膝关节滑液以ELISA法测IL-1β、TNFα水平;缺口末端标记法(TUNEL)标记检测凋亡。结果:TUNEL标记显示阴性对照组、阳性对照组、rhTNFR:Fc组的凋亡细胞分别为(2.1±0.9)%、(3.9±0.5)%和(4.4±0.8)%。阳性对照组和rhTNFR:Fc组膝关节滑液IL- 1β、TNF-α水平显著下降。结论:本试验首次阐明了rhTNFR:Fc可诱导CIA大鼠滑膜细胞的凋亡。抗类风湿性关节炎机制可能通过诱导滑膜细胞凋亡,最终减轻CIA大鼠的关节炎症。

Objective： To investigate the effect of RhTNFR：Fc for synovlocytes apoptosis in collagen induced arthritis（CIA） rats model. Method： The rats of rhTNFR ： Fc group were administered with rhTNFR： Fc at 1.75 μg per 100 g ih everyday, The rats of positive group were administered with methotrexate（ MTX）, The rats of negative group were administered with 0.9% NS ih respectively. The rats were killed on the 31st day after the rhTNFR： Fc administration. The synovium were studied by TUNEL, then IL-1 β,TNF-α concentration were measured. Result： The TUNEL labeling demonstrated that the percentage of apoptotic cells was （2.1 ± 0.9 ）% in the negative group, （ 3.9 ± 0. 5 ） % in the positive group and （4.4 ± 0. 8 ） % in rhTNFR ： Fc group. The difference of apoptotic rats between the rhTNFR：Fc and the negative group was significant （P 〈 0. 01 ）. The IL-1 β ,TNF-α concentration from synovial fluid were significant reduced in RhTNFR：Fc group. Condusion： It is first proved that rhTNFR：Fc can induce synoviocytes apoptosis in CIA rats. That induce synoviocytes apoptosis may be one of the rhTNFR ： Fc mechanisms in treating RA. rhTNFR： Fc may induce apoptosis of synoviocytes by which it can relieve joint inflammation of CIA rats.