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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 recombinant human tumor necrosis factor receptor fusion protein (rhTNFR: Fc) on the apoptosis of synovial cells induced by collagen in the Wistar rats with rheumatoid arthritis (CIA). Methods: The model was randomly divided into negative control group, positive control group and rhTNFR: Fc group. rhTNFR: Fc group was injected subcutaneously (ih) once every day at 17.5μg · kg -1; 0.9% sodium chloride solution at the same time as ih in negative control group; methotrexate every d ih in positive control group, Thirty days later, synovial fluid of knee joint was extracted for determination of IL-1β and TNFα by ELISA. Apoptosis was detected by nick-end labeling (TUNEL). Results: TUNEL staining showed that apoptotic cells in the negative control group, positive control group and rhTNFR: Fc group were (2.1 ± 0.9)%, (3.9 ± 0.5)% and (4.4 ± 0.8)%, respectively. The positive control group and rhTNFR: Fc group synovial synovial fluid IL-1β, TNF-α levels decreased significantly. Conclusion: This experiment first demonstrated that rhTNFR: Fc can induce the apoptosis of synoviocytes in CIA rats. The anti-rheumatoid arthritis mechanism may eventually reduce synovial inflammation in CIA rats by inducing synovial cell apoptosis.