非T细胞结合肽(FNS007)对胶原诱导型大鼠关节炎的影响

摘要

目的:探讨非T细胞结合肽(FNS007)对大鼠Ⅱ型胶原(Collagen typeⅡ,CⅡ)诱导的关节炎(Collagen-induced arthritis,CIA)的影响及可能机制.方法:以牛CⅡ免疫Lewis大鼠诱发CIA模型后,随机分为模型组、FNS007低(0.25 mg/kg)、中(0.5 mg/kg)、高(1.0 mg/kg)剂量组及阳性药(甲氨蝶呤)组,另设空白对照组,尾静脉注射相应药物,隔天一次,空白对照组及模型组大鼠给予溶媒磷酸盐缓冲液(Phosphate buffered solution,PBS).实验期间观察踝关节宽度以及爪厚度,关节炎评分.给药后第22天处死大鼠,ELISA法测定血清中TNF-α、IFN-γ和IL-6的水平及抗CⅡ抗体水平;X光分析FNS007对CIA大鼠后爪骨损伤的疗效,并对大鼠踝关节进行组织病理学检查.结果:FNS007 高剂量明显抑制CIA大鼠足爪肿胀程度,爪厚度和踝关节宽度明显降低;炎症评分明显降低;血清促炎性细胞因子TNF-α、IFN-γ、IL-6的含量和抗CⅡ抗体的水平明显降低;X光评分和组织病理评分明显降低.FNS007 中剂量和低剂量组的以上指标也有不同程度的改善.结论:FNS007对大鼠CIA具有治疗作用,其机制与其抑制T细胞活化,抑制CIA大鼠体内抗CⅡ 的产生,并降低促炎性细胞因子TNF-α、IFN-γ、IL-6的含量,从而抑制异常免疫反应有关.%Objective:To observe the effects of FNS007 on collagen Ⅱ-induced arthritis(CIA) rat models and investigate the underlying mechanism.Methods: CIA model was induced by intradermal injection of Freunds adjuvant and bovine CⅡ.Rats were randomly divided into six groups:normal control group,model group,methotrexate group,high,middle and low doses of FNS007 groups,with 12 rats in each group.FNS007 was gived by intravenous injection,the normal control and model group were administrated with PBS.Observing the paw thickness,ankle joint width and the arthritis scores in the CIA rats during the experiment.On d 22 after injection of the drug, all rats were killed.Interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6) and level of anti-CⅡantibody in serum were examined by enzyme-linked immunosorbent assay (ELISA).The pathological score and radiography of ankle joint were evaluated.Results: Data revealed that FNS007 treated groups showed a significant reduction in paw thickness,ankle joint width and the arthritis scores compared to model group (P<0.05,P<0.01),especially FNS007 high dose goup.The levels of TNF-α,IFN-γ,IL-6 and anti-CⅡantibodies in serum in high dose goup were significantly lower than those of model group(P<0.05,P<0.01).X-ray examination showed that FNS007 could significantly alleviate the damage of joint and decrease the radiographic scores.Pathological examination exhibited that FNS007 could significantly reduce pathological scores,alleviate inflammatory cell infiltration and synovial hyperplasia,improve the histopathological changes.Conclusion: FNS007 has a treating effect on CIA rats,and the mechanisms may be through competitive inhibition of T cell,inhibiting inflammatory cytokines and anti-CⅡantibodies secretion,regulating the abnormal immune responses.