非T细胞结合肽(FNS007)对Ⅱ型胶原所诱导大鼠关节炎的预防作用

Prophylactic effects of non-T cell binding peptide-FNS007 on type 2 collagen-induced arthritis in rats

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。

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-Ⅱcollagen 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(0.25mg/kg),FNS007 middle dose group(0.5mg/kg)and FNS007 high dose group(1.0mg/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-1βin model group were significantly higher than those in blank control group(P<0.05).Furthermore FNS007 could significantly decrease the serum levels of TNF-αand IL-1βof 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.