大鼠胶原诱导关节炎应用来氟米特的时间治疗学研究

Research on leflunomide chronotherapy in treatment of collagen-induced arthritis in rats

目的探讨来氟米特(LEF)不同给药时间对大鼠胶原诱导关节炎的治疗效果和对炎性细胞因子的影响。方法取6只大鼠作为空白组,其余造模后第15天加强免疫后关节炎指数>5的24只成模大鼠随机分为模型组、LEF7时组、LEF19时组,每组8只。LEF7时组于7:00、LEF19时组于19:00分别灌胃LEF 5 mg/(kg·d),模型组及空白组分别给予等量生理盐水,均灌胃28 d。对比观察各组胶原诱导关节炎模型炎症评分、外周血肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平及骨质破坏情况。结果给药后LEF7时组、LEF19时组关节炎指数、关节肿胀度均明显低于给药前及模型组(P均<0.05),LEF19时组有高于LEF7时组趋势,但2组比较差异无统计学意义(P>0.05)。LEF7时组、LEF19时组外周血TNF-α、IL-6水平均低于模型组(P均<0.05);LEF19时组TNF-α和IL-6水平有高于LEF7时组的趋势,但2组比较差异无统计学意义(P均>0.05)。各组胶原诱导关节炎大鼠关节均出现明显的骨质破坏,且模型组骨质破坏更明显。结论 LEF不同时间给药对大鼠胶原诱导关节炎及其炎性细胞因子的影响可能存在差异,且可能延缓骨质破坏。

Objective It is to investigate the therapeutic effect of leflunomide （LEF） by different administration time in rats with collagen-induced arthritis （CIA） and its influence on inflammatory cytokines. Methods 6 rats were selected into the control group, and the others were used to establish the models of CIA, and 24 successful models were randomly divided into model group, group A and group B with 8 cases in each groups. LEF was given at 07：00 in group A and 19：00 in group B re- spectively, and equal dose of physiological saline was given in control group and model group. Gastric administration lasted 28 days. Then the changes of inflammation scores, tumor necrosis factor alpha （ TNF - α） , interleukin - 6 （ IL - 6） levels of pe- ripheral blood in all groups were observed, and the X - ray changes of joints were observed too. Results The arthritis indexes （AI） and joint swelling degree were significantly decreased in the group A and group B after treatment （all P 〈 0.05 ） , and there was significant difference compared with model group （ all P 〈 0.05 ） , there was a trend of that in group A was lower than that in group B, but there was no significant difference between group A and group B （ all P 〉 0.05 ）. Compared with model group, the levels of TNF - α, IL - 6 in peripheral blood were significantly decreased in group A and group B （ all P 〈 0. 05 ） , there was a trend of that in group A was lower than that in group B, but there was no significant difference between group A and group B （all P 〉 0. 05）. Bone destruction and loss were observed in all rats of CIA, and the bone destruction in model group was the most obvious. Conclusion The influence of LEF administration at different time on CIA and inflammatory cyto- kines in rats may be different. LEF may be prevented bone destruction in CIA rats.