佐剂性关节炎大鼠外周血TNF-α、IL-1β、MIF与MLT的昼夜节律

Circadian Rhythm of TNF-α,IL-1β,MIF and MLT in Peripheral Blood of Rats with Adjuvant Arthritis

目的观察佐剂性关节炎(AA)大鼠外周血肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、巨噬细胞移动抑制因子(MIF)和褪黑素(MLT)水平的昼夜变化。方法采用Wistar大鼠复制AA模型,光、暗周期L∶D=12∶12;于造模后第19天08:00、12:00、16:00、20:00、24:00、04:00共6个时间点采集尾静脉血,采用ELISA法检测TNF-α、IL-1β、MIF、MLT含量,余弦法分析其昼夜节律。造模前与造模后6个时间点采用容积测量仪检测大鼠双侧足爪容积。结果 AA大鼠足爪容积未发现明显昼夜变化(P>0.05)。昼夜不同时间点外周血细胞因子TNF-α、IL-1β、MIF、MLT水平的波动具有统计学意义(P<0.05);4种细胞因子昼夜节律特征相似,即峰值相位均位于夜间(暗期),其中MIF的峰值出现时间较早,谷值相位均位于白天(明期)。结论 AA大鼠外周血TNF-α、IL-1β、MIF与MLT的表达存在昼夜节律,提示生物钟在类风湿关节炎的病理生理及治疗研究中具有重要意义。

Objective To observe the circadian changes of tumor necrosis factor-alpha （ TNF-α） , interleukin-1 beta （ IL-1β） , macrophage migration inhibitory factor （ MIF） and melatonin （ MLT） in peripheral blood of rats with adju-vant arthritis （ AA） . Methods The AA models of Wistar rats were established, and light-dark cycle was L∶ D=12∶12;19th d after modeling, the tail venous blood was collected at 08：00, 12：00, 16：00, 20：00, 24：00 and 04：00. The contents of TNF-α, IL-1β, MIF and MLT were detected by ELISA assay, and the circadian rhythm was analyzed by co-sine method. The hibateral paws volumes of rats were detected using the volume measuring instrument before modeling and at the 6 time points after modeling, and the swelling rates were calculated. Results There was no significant diurnal variation in the paws volumes of AA rats （P〉0. 05）. The changes in levels of TNF-α, IL-1β, MIF and MLT of periph-eral blood were statistically significant （P〈0. 05）; characteristics of circadian rhythm in the 4 cytokines were similar, namely the peak phase was located at night （ dark） , in which the peak of MIF appeared earlier, and valley phase was lo-cated in the daytime （ light） . Conclusion The expressions of TNF-α, IL-1β, MIF and MLT of peripheral blood in AA rats show the circadian rhythm, which suggests that the biological clock may be important in the pathophysiology and treatment of rheumatoid arthritis.