【摘要】 背景:研究表明,多种细胞因子与炎症递质参与类风湿关节炎的致病过程,沙利度胺作为一种免疫调节剂应用于风湿性疾病的治疗。目的:观察沙利度胺对胶原诱导型关节炎大鼠的关节炎症及血浆肿瘤坏死因子α表达的影响。方法:将Wistar大鼠随机分为4组。除正常对照组外,其余3组多点皮内注射Ⅱ型胶原与完全弗氏佐剂的乳化剂诱导出关节炎模型。从免疫后第10天开始,正常对照组和单纯造模组大鼠给予蒸馏水灌胃;沙利度胺组给予沙利度胺灌胃;甲氨蝶呤组给予甲氨蝶呤灌胃。实验前及实验7,14,21,28,35,42,60d测定各组的大鼠不同时间点的足爪厚度、血浆肿瘤坏死因子α浓度,进行踝关节病理评分和放射学检查。结果与结论:沙利度胺可以有效减轻胶原诱导型性关节炎大鼠足爪肿胀程度,造模后第28天单纯造模组足爪厚度值大于沙利度胺组(P<0.05)。与造模组比较,沙利度胺组肿瘤坏死因子α浓度在造模后14d降低(P<0.05)。沙利度胺组14~60d病理积分均显著低于造模组;沙利度胺组出现骨骼改变的平均时间明显晚于单纯造模组(P<0.01),且关节破坏程度较轻。沙利度胺组和甲氨蝶呤组各指标差异无显著性意义。结果证实,沙利度胺可以通过影响肿瘤坏死因子α的表达,抑制滑膜炎症及周围组织破坏,有效减轻胶原诱导型性关节炎大鼠关节的炎症程度。更多还原

【Abstract】 BACKGROUND: Previous research has demonstrated that multiple cytokines and inflammatory transmitters participate in pathopoiesis of rheumatoid arthritis. Thalidomide was an immunomodulator which used to treat rheumatoid disease. OBJECTIVE: To study the effect of thalidomide on inflammatory arthropathy and tumor necrosis factor-alpha (TNF-α) expression in a rat model of collagen induced arthritis (CIA). METHODS: Wistar rats were randomly divided into 4 groups. All rats except the normal group were intradermally injected with the emulsion of type II collagen and complete Freund’s adjuvant to induce arthritis model. After 10 days, rats of normal group and model group were given an intragastric administration with distilled water, rats of thalidomide group were given an intragastric administration with thalidomide, and rats of methotrexate (MTX) group were given an intragastric administration with MTX. The thickness of the claws and the concentration of TNF-α were measured or detected before and at 7, 14, 21, 28, 35, 42, and 60 days after operation, and the pathological score and radiography of ankle joint were evaluated. RESULTS AND CONCLUSION: Thalidomide effectively relieved swelling of ankle joint of CIA rats. On the 28th day, the thickness of the claws of the model group was significantly greater than of thalidomide group (P < 0.05). To compare with model group, the concentration of TNF-α in blood plasma decreased after 14 days in thalidomide group (P < 0.05). The pathological scores of the thalidomide group were significantly less than of model group between 14 and 60 days. The time of osteoclasia in thalidomide group was later than of model group (P < 0.01), and the degree of osteoclasia was milder. There was no significant difference between thalidomide and MTX groups. Thalidomide can effectively lighten disease progression in the CIA rats through influencing TNF-α expression and suppressing synovitis and histoclasia in the joint.更多还原