文章摘要
陈晓明1 游运辉2 罗卉2 贺立新3,4.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[J].,2011,11(17):3266-3269
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
Effects of the Combined Use of Leflunomide with Etanercept on ImmuneFunction in Rat Adjuvant Arthritis
  
DOI:
中文关键词: 类风湿关节炎  来氟米特  依那西普  白细胞介素-1  肿瘤坏死因子  基质金属蛋白酶-3
英文关键词: Rheumatoid arthritis  Leflunomide  Etanercept  IL-1  TNF  MMP-3
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作者单位
陈晓明1 游运辉2 罗卉2 贺立新3,4 湖南省邵阳市中心医院 
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中文摘要:
      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。
英文摘要:
      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 control group (P<0.01). After administration, the levels significantly decreased in the three groups (P<0.01), especially in LEF+Etanercept 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.
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