非T细胞结合肽(FNS007)对关节炎小鼠病程及骨损伤的影响  

Effects of non-T cell binding peptide (FNS007) on disease progression and bone destruction in a mouse model of collagen-induced arthritis

作　　者：李立萍[1] 刘超 钟志伟[3] 解丽君[1] 黄丽晶[2] 郝娜[1] 葛兰 闫少峰 李国风[1] 许晓红 张勤增[1] 李兰芳[1] 姜红[1] 张建新[1] 

机构地区：[1]河北省疾病预防控制中心药物研究所,石家庄050021 [2]河北菲尼斯生物技术有限公司,石家庄050035 [3]河北医科大学第三医院放射科,石家庄050051

出　　处：《免疫学杂志》2017年第6期492-496,共5页Immunological Journal

基　　金：河北省重大医学科研课题(zd2013069);河北省科技支撑计划(14272608D)

摘　　要：目的观察非T细胞结合肽(FNS007,又称NTAP)对Ⅱ型胶原(collagen typeⅡ,CⅡ)诱导的关节炎(collagen-induced arthritis,CIA)小鼠炎症反应及骨损伤的影响,并探讨其作用机制。方法采用Ⅱ型胶原诱导建立CIA小鼠模型。发病小鼠随机分为模型组、FNS007 1.2、2.4、4.8 mg/kg(低、中、高)剂量组及阳性药阿巴西普(5 mg/kg)组,另设正常对照组,尾静脉注射给药,隔天1次,直至治疗结束。给药后第28天处死小鼠。给药期间每日评价各组小鼠四爪的关节炎临床评分;治疗结束后,通过X光、显微计算机断层扫描(micro-computed tomography,Micro-CT)及三维重建对小鼠四爪进行骨损伤评价以及骨参数分析。结果与模型组比较,FNS007明显降低CIA小鼠关节炎临床炎症评分;X光结果显示,FNS007明显减轻CIA小鼠四爪骨损伤程度;FNS007组小鼠micro-CT评分及骨表面积与骨体积比(BS/BV)明显降低,组织矿物质密度(TMD)及骨小梁厚度(Tb.Th)明显升高。结论 FNS007可明显抑制胶原性关节炎小鼠的关节炎症,改善关节组织损伤和骨破坏。This study performed to study the effect of non-T cell binding peptide （FNS007） on inflammation, bone and joint destruction in mice of collagen -induced arthritis （CIA）. The CIA model was induced by intradermal injection micell of bovine C Ⅱ ＋ Freunds adjuvant. At the clinical onset of CIA, mice were randomly divided into 6 groups： normal control group （control）, model group, ORENCIA （Abataeept） 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. Mice in control group were given vehicle as well as in CIA group, mice in the other groups were treated with FNS007 or Abatacept on the onset of CIA every other day until the study was terminated on day 28 after injection of the drug. Clinical scores in the CIA mice was observed during the experiment. At the experimental endpoint, bone destruction, the bone surface area/bone volume ratio, tissue mineral density and trabecular thickness were determined using X-ray imaging and microcomputed tomography （micro-CT） scanning and three-dimensional reconstruction. Data revealed that compared with control group, clinical scores were increased in CIA group （P〈0.01）, and FNS007 could significantly reduce clinical score. Radiographic examination and Micro-CT data showed that FNS007 could significantly reduce radiographic bone erosions, suppress structural joint damage. Tissue mineral density and trabecular thickness in CIA group were significantly lower than those in control group （P〈0.01）, while bone surface area/bone volume ratio was significantly higher than that in control group （P〈0.01）; compared with CIA group, tissue mineral density and trabecular thickness were increased, while bone surface area/bone volume ratio was significantly decreased in FNS007 groups. In conclusion, FNS007 significantly inhibits the disease progression in CIA mice, with reductions in inflammation and bone and joint destruction.

关 键 词：胶原诱导型关节炎 小鼠 非T细胞结合肽(FNS007) 微焦点计算机断层扫描 

分 类 号：R593.22[医药卫生—内科学]