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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),用药后各组的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水平,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。
Objective: To study the therapeutic effect of leflunomide and etanercept on adjuvant arthritis (AA) rats and its possible mechanism. Methods: The model of arthritis in AA rats was established and divided into normal control group, model group, leflunomide group, etanercept group and leflunomide combined with etanercept group. The arthritis index score method The level of IL-1β and TNF-α in synovial tissue and serum were detected by semi-quantitative RT-PCR and radioimmunoassay. The content of MMP-3 in synovial tissue was detected by immunohistochemistry. Results: (1) Compared with AA model group, the AI scores of leflunomide group, etanercept group and compatibility group were significantly decreased (P <0.01), and the arthritis index of compatibility group was the lowest (P <0.05). ② The levels of IL-1β and TNF-α in the serum and synovial tissue of the model group were significantly higher than those in the normal control group (P <0.01), and the levels of IL-1β and TNF-α in the model group were decreased (P <0.01 or P <0.05). ③The positive expression of MMP-3 in synovial tissue of the model group was significantly higher than that of the normal control group (P <0.01). After treatment, the expression of MMP-3 The positive density decreased (P <0.01), of which the compatibility group was significantly lower than the leflunomide group and etanercept group (P <0.01). Conclusion: The combination of leflunomide and etanercept can obviously alleviate the arthritis of AA rats, decrease the level of IL-1β and TNF-α in serum and synovial tissue and decrease the expression of MMP-3 in synovium Better than leflunomide or etanercept alone.