来氟米特对大鼠佐剂性关节炎的时间治疗学初步观察

Rudiment Observation of Leflunomide Chronotherapy in Treatment of Adjuvant Arthritis in Rats

目的探讨来氟米特(LEF)不同给药时间对大鼠佐剂性关节炎的治疗效果和对炎性细胞因子的影响。方法建立大鼠佐剂性关节炎模型,于9时和21时两个昼夜不同时间应用LEF 18 d,对比观察佐剂性关节炎模型炎症评分及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)水平的变化。结果 LEF两个时间用药组关节炎指数和关节肿胀均明显下降,与用药前和模型组相比具有统计学差异(P<0.05),在关节肿胀抑制率方面显示LEF21时给药优于9时给药的趋势,但无统计学差异(P>0.05)。不同时间应用LEF均可显著下调外周血TNF-α、IL-1β、MIF、MLT表达(P<0.05);LEF21时组IL-1β水平明显低于LEF9时组(P<0.05),其他细胞因子在两个时间用药组之间无明显差别(P>0.05)。结论 LEF不同时间给药对大鼠佐剂性关节炎及其炎性细胞因子的影响可能存在差异,有待进一步研究。

Objective To investigate the effect of leflunomide （LEF） by different administration times on thera- peutic effect and inflammatory cytokines in rats with adjuvant arthritis （AA）. Methods Rat models of AA had been es- tablished, and 18 successful models were randomly divided into model group, group A and B （ n = 6）. LEF was given at 09：00 （group A） and 21：00 （group B） respectively for 18 days, and then the level changes of inflammation score, tumor necrosis factor alpha （TNF- ct）, interleukin -1 beta （IL-1 ~） , macrophage migration inhibitory factor （MIF） and melatonin （MLT） of peripheral blood in the two groups were observed. Results Indexes of arthritis and joint swelling were significantly decreased in the group A and B, and the differences in the indexes before and after treatment in the group A and B, and compared with those in model group were statistically significant （ P 〈 0. 05 ） ; inhibition ratio of joint swelling in group B was better than that in group A, but the difference was not statistically significant （P 〉 0.05 ）. Levels of TNF- ct, IL-1 6, MIF and MLT in peripheral blood could be significantly decreased by using LEF at different times; IL-1 [~ level in group B was significantly lower than that in group A （P 〈 0. 05）, but other cytokines showed no signifi- cant differences by using LEF at different times （P 〉 0. 05 ）. Conclusion The Effect of LEF administration at different times on adjuvant arthritis and inflammatory cytokines in rats may be different, but it need to be further researched.