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 investigate the effect and possible mechanism of non-T cell binding peptide (FNS007) on collagen-induced arthritis (CIA) induced by Collagen typeⅡ (CⅡ) in rats. Methods: CIA model was induced in Lewis rats induced by bovine CⅡ and then randomly divided into model group, FNS007 low dose (0.25 mg / kg), medium dose (0.5 mg / kg) and high dose (1.0 mg / kg) Methotrexate). A blank control group was also established. The corresponding drugs were injected through the tail vein, and once a day, the blank control group and model group rats were given phosphate buffered solution (PBS). Ankle width and paw thickness, arthritis score were observed during the experiment. The rats were sacrificed on the 22nd day after administration, the levels of TNF-α, IFN-γ and IL-6 in the serum and the level of anti-CⅡ antibody were measured by ELISA; the effect of FNS007 on the hind paw bone injury in CIA rats was analyzed by X-ray Histopathological examination of rat ankle joint. Results: FNS007 high dose significantly inhibited the degree of claw swelling in paws of CIA rats, the paw thickness and the ankle joint width were significantly decreased, the inflammatory score was significantly decreased, the levels of serum proinflammatory cytokines TNF-α, IFN-γ and IL-6 The level of CⅡantibody decreased obviously; X-ray score and histopathological score decreased significantly. FNS007 medium and low dose group of the above indicators also have varying degrees of improvement. CONCLUSION: FNS007 has a therapeutic effect on CIA in rats. Its mechanism is that it inhibits the activation of T cells, inhibits the production of anti-CⅡ in CIA rats, and decreases the levels of pro-inflammatory cytokines TNF-α, IFN-γ and IL- Thus inhibiting the abnormal immune response.