神经肽FF对类风湿关节炎小鼠模型的治疗作用研究

On the Therapeutic Effect of NPFF on Mouse Models with Rheumatoid Arthritis

目的:探讨神经肽FF(NPFF)对类风湿关节炎DBA/1小鼠模型的治疗作用。方法:将30只DBA/1小鼠随机分为胶原诱导性关节炎(CIA)模型组、NPFF治疗组、健康对照组,每组10只。CIA模型组和NPFF治疗组利用牛Ⅱ型胶原诱导法建立小鼠类风湿关节炎模型,造模后,NPFF治疗组小鼠腹腔注射NPFF 30 mg·kg^(-1),每周3次,连续2周。CIA模型组腹腔注射同体积的生理盐水作为对照。治疗结束后对小鼠关节炎指数进行评分,检测各组小鼠血清中细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-17的含量水平,取小鼠后足踝关节进行病理学观察及评分。结果:与CIA模型组比较,NPFF治疗的CIA小鼠能够明显减轻CIA小鼠的临床症状;明显抑制CIA小鼠多发性关节炎的发生(P=0.004);显著降低小鼠血清TNF-α(P=0.000)、IL-1β(P=0.001)和IL-17(P=0.001)的含量水平;减少滑膜细胞增殖(P=0.010)、炎性细胞浸润(P=0.007)、血管翳产生(P=0.005)、炎症(P=0.002)和骨质侵蚀(P=0.003)的发生。结论:NPFF对DBA/1小鼠类风湿关节炎具有治疗作用,血清中炎性细胞因子TNF-α、IL-1β和IL-17的显著降低是NPFF治疗类风湿关节炎可能的作用机制。

Objective：To investigate the therapeutic effect of neuropeptide FF（NPFF）on DBA/1 mice models with rheumatoid arthritis.Methods：Thirty DBA/1 mice were randomly divided into a collagen-induced arthritis（CIA）model group,an NPFF treatment group and a healthy control group,with 10 mice in each. In the CIA model group and NPFF treatment group,the models of rheumatoid arthritis were induced by bovine type II collagen.After modeling,the mice in the NPFF treatment group were given an intraperitoneal injection of 30 mg·kg-1 NPFF,3 times per week for 2 weeks.While those in the CIA model group were given an intraperitoneal injection of the same volume of normal saline.After treatment,scores were made on mice arthritis index,and the levels of tumor necrosis factor-α（TNF-α）,interleukin（IL）-1β and IL-17 in serum were detected.Ankle joints of mouse’s pleopoda were isolated for pathological observation and scoring.Results：Compared with the CIA model group,clinical symptoms of CIA mice treated with NPFF were signiifcantly improved;the occurrence of polyarthritis in CIA mice was obviously inhibited（P=0.004）;the contents of TNF-α（P=0.000）,IL-1β（P=0.001）and IL-17（P=0.001）were signiifcantly reduced;and synoviocyte proliferation（P=0.010）, inflammatory cell infiltration（P=0.007）,pannus generation（P=0.005）,inflammation（P=0.002）and bone erosion（P=0.003）were decreased.Conclusion：NPFF has a therapeutic effect on rheumatoid arthritis in DBA/1 mice,and the signiifcant reduction of inlfammatory cytokines TNF-α,IL-1β and IL-17 in serum may be the mechanism of treating rheumatoid arthritis with NPFF.