中国药理学通报2017，Vol.33Issue(5)：611-616,6.DOI:10.3969/j.issn.1001-1978.2017.05.005
非T细胞结合肽(FNS007)对小鼠胶原性关节炎的抑制作用及其机制
Inhibition and mechanisms of non-T cell binding peptide(FNS007)in collagen Ⅱ-induced arthritis mice models
摘要
Abstract
Aim To investigate the effect of non-T cell binding peptide(FNS007)on collagen type Ⅱ-induced arthritis(CIA)in mice and the possible mechanisms.Methods The CIA model was induced by intradermal injection of bovine CⅡ+Freunds adjuvant.At the clinical onset of CIA,mice were randomly divided into 6 groups: blank control group(Control),model group,ORENCIA(abatacept)group,FNS007 low dose(1.2 mg·kg-1)group,FNS007 middle dose(2.4 mg·kg-1)group and FNS007 high dose(4.8 mg·kg-1)group.FNS007 was given by intravenous injection on the first day of arthritis and every other day until the study was terminated on d 28 after injection of the drug.The paw thickness and the ankle joint width were measured,and the arthritis scores were recorded.At termination,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and level of anti-CⅡ antibody in serum were examined by enzyme-linked immunosorbent assay(ELISA).Bone injury was analyzed by X-ray imaging,and HE staining was conducted to observe the histopathologic changes and pathological score of ankle tissues.Results CIA models were successfully induced.Compared with CIA group,FNS007 high dose significantly reduced the paw thickness and the ankle joint left-right diameter,lowered arthritis scores in CIA mice,reduced serum concentrations of IFN-γ,IL-6 and anti-CⅡ antibodies,and lowered the radiographic and histologic scores.Compared with CIA group,FNS007 middle dose group showed marked reduction in the arthritis scores,IL-6 content in serum,and inhibion in the radiographic and histologic scores.The arthritis scores,concentration of IFN-γ,the radiographic and histologic scores were significantly reduced in FNS007 low dose group compared with those in model group.Conclusion FNS007 can effectively inhibit the progression of CIA through inhibiting T-cell activation and reducing inflammatory cytokines,anti-CⅡ antibodies,and histoclasia and bone destruction.关键词
胶原诱导性关节炎/类风湿关节炎/小鼠/炎症因子/抗Ⅱ型胶原抗体/Ⅱ型胶原Key words
collagen-induced arthritis/rheumatoid arthritis/mice/inflammatory factors/anti-CⅡantibody/type Ⅱ collagen分类
医药卫生引用本文复制引用
李立萍,张勤增,姜红,李兰芳,张建新,解丽君,郝娜,李国风,刘超,黄丽晶,葛兰,闫少峰,许晓红..非T细胞结合肽(FNS007)对小鼠胶原性关节炎的抑制作用及其机制[J].中国药理学通报,2017,33(5):611-616,6.基金项目
河北省重大医学科研课题资助项目(Nozd2013069) （Nozd2013069）
河北省科技支撑计划项目(No14272608D) （No14272608D）
