【摘要】 目的探讨非T细胞结合肽(FNS007)对Ⅱ型胶原诱导的大鼠胶原性关节炎(CIA)的预防作用及机制。方法用牛Ⅱ型胶原(CⅡ)同不完全弗氏佐剂配制的乳剂诱发Lewis大鼠CIA模型。在诱发的同时腹腔注射给予FNS007低、中、高(0.25、0.5、1 mg/kg,1次/周)剂量,甲氨蝶呤组(MTX 0.5 mg/kg,2次/周)作为阳性对照。另设模型组和空白对照组。给药期间测量大鼠体重和爪厚度;进行关节炎评分;实验结束后腹主动脉取血,酶联免疫吸附法(ELISA)检测血清细胞因子水平;进行病理组织学检查。结果与模型组比较,FNS007各剂量组体重均显著增加(P<0.05);FNS007高剂量组的爪厚度及炎症评分曲线下面积较模型组显著降低(P<0.05);各给药组病理学损伤均较模型组明显减轻(P<0.05);模型组大鼠血清中TNF-α和IL-1β水平显著高于空白组(P<0.05),FNS007显著降低CIA大鼠血清中TNF-α和IL-1β水平(P<0.05)。结论 FNS007预防给药能明显减轻CIA症状。更多还原

【Abstract】 Objective To investigate the pro phylactic effects and action mechanism of non-T cell binding peptide( FNS007) on type 2 collagen-induced arthritis in rats. Methods The CIA models of Lewis rats were established by intradermal injecting bovine type-Ⅱ collagen with incomplete Freund’s adjuvant. The rats were randomly divided into six groups: blank control group,model group,methotrexate( MTX) group,FNS007 low dose group( 0. 25 mg/kg),FNS007 middle dose group( 0. 5 mg/kg) and FNS007 high dose group( 1. 0 mg/kg),with 10 rats in each group. The rats in FNS007 low dose,middle dose and high dose groups were injected with different dose FNS007 respectively,at the same time of induction of CIA,once a week for 5 weeks. The rats in MTX group were injected with methotrexate and,twice a week for 5 weeks. The body weight,hind-paw swelling,arthritis scores,and histologic analysis were evaluated,moreover,the serum levels of cytokines were detected by enzyme-linked immunosorbent assays( ELISA) and histopathologic examination was performed. Results As compared with those in model group,the body weight was significantly increased in three doses FNS007 group( P < 0. 05). Moreover the radiographic scores in three FNS007 groups and MTX group were significantly lower than those in modeel group( P < 0. 05). Histopathological examination showed that FNS007 could obviously relieve the inflammation,pannus formation and damage of cartilage. In addition the serum levels of TNF-αand IL-1β in model group were significantly higher than those in blank control group( P < 0. 05). Furthermore FNS007 could significantly decrease the serum levels of TNF-α and IL-1β of rats with CIA( P < 0. 05). Conclusion The prophylactic administration of FNS007 can significantly relieve symptoms of CIA in rats,and its action mechanism may be correlated with inhibiting T-cell activation.更多还原