来氟米特联合依那西普对佐剂性关节炎大鼠免疫功能的影响

目的：研究来氟米特和依那西普联合使用对佐剂性关节炎（AA）大鼠的治疗作用及其可能的作用机制。方法：建立AA大鼠关节炎模型，分为正常对照组、模型组、来氟米特组、依那西普组、来氟米特联合依那西普配伍组；采用关节炎指数评分法评价大鼠关节炎症程度，半定量RT-PCR和放射免疫法检测滑膜组织及血清中IL-1β、TNF-α表达水平，免疫组化方法检测滑膜组织中MMP－3含量。结果：①相较于AA模型组，来氟米特组、依那西普组和配伍组中大鼠的AI评分均显著下降（P〈0．01），其中以配伍组关节炎指数为最低（P〈0．05）。②模型组大鼠血清及滑膜组织的IL-1β和TNF-α水平明显高于正常对照组（P〈0．01），用药后各组的IL-1β和TNF-α水平均有所下降，并以配伍组降低最为明显（P〈0．01或P〈0．05）；③模型组大鼠滑膜组织MMP-3表达阳性密度显著高于正常对照组（P〈0．01），用药后备组的MMP-3阳性密度降低（P〈0．01），其中配伍组下降程度明显高于来氟米特组和依那西普组（P〈0．01）。结论：来氟米特和依那西普联合使用可明显减轻AA大鼠的关节炎症，降低血清和滑膜组织中IL-1β和TNF-α平，减少滑膜中MMP-3的表达，疗效优于单独使用来氟米特或依那西普。

Effects of the Combined Use of Leflunomide with Etanercept on Immune Function in Rat Adjuvant Arthritis

Objective： To study the therapeutic effects of Leflunomide （LEF） combined with Etanercept on rat adjuvant arthritis （AA）, as well as the possible mechanism. Methods： Established the rat model of collagen-induced arthritis, and the rats were divided into control group, AA model group, LEF group, Etanercept group and LEF＋Etanercept group; Arthritis were evaluated by arthritis index, and semi-quantitative RT-PCR, radioimmunoassay and immunohistochemistry were respectively used to detect the levels of IL-1β , TNF-α and MMP-3 in synovium and serum. Results： ① The arthritis index of AA model group was significantly higher than those of LEF group, Etanercept group and LEF＋Etanercept group （P〈0.01）, and the arthritis index was significantly lowest in LEF＋Etanercept group （P〈0.05）. ② The levels of IL-1β and TNF-α in synovium and serum were notably higher in AA model group than those in con- trol group （P〈0.01）. After administration, the levels significantly decreased in the three groups （P〈0.01）, especially in LEF＋Etanereept group （P〈0.05）. ③The positive expression of MMP-3 in synovium of model group was significantly higher that that of control group. （P〈0.01）. The positive expression of MMP-3 in each group was lowered after administration. Compared with LEF group and Etanercept group, the positive expression of MMP-3 was significantly lower in LEF＋Etanercept group （P〈0.01）. Conclusions： The combined use of LEF and Etanercept can significantly relieve the arthritis syndrome in AA rats by decreasing the expression of IL-1β and TNF-α in synovium and serum, as well as that of MMP-3 in synovium, which is better than LEF or Etanercept used separately.