沙利度胺联合甲氨蝶呤对关节炎大鼠炎症及细胞因子的影响

Effect of thalidomide combined with methotrexate on the inflammation and cytokines of rats with collagen type Ⅱ induced arthritis

目的:研究沙利度胺联合甲氨蝶呤对大鼠II型胶原诱导型关节炎症及细胞因子的影响。方法:建立类风湿性关节炎大鼠模型,自造模次日治疗组分别给予沙利度胺(150mg·kg-1.d-1)联合甲氨蝶呤(0.2mg·kg-1.d-1)和甲氨蝶呤(0.2mg·kg-1.d-1)单用,疗程均为6周。各组大鼠每周进行一次关节炎指数(AI)评分,于造模第6周取血清进行WesternBlot检测大鼠体内IL-1β、TNF-α的表达并计算相对含量。结果:沙利度胺联合甲氨蝶呤、单用甲氨蝶呤均能降低模型大鼠AI评分,沙利度胺联合甲氨蝶呤作用强于单独使用甲氨蝶呤,使AI评分明显下降。沙利度胺联合甲氨蝶呤、甲氨蝶呤均可抑制IL-1β、TNF-α的表达,治疗后两种因子表达均与模型组有统计学差异(P<0.05),但仍不能达到正常水平(P<0.05)。结论:沙利度胺联合甲氨蝶呤可能通过抑制IL-1β、TNF-α的表达而达到抗关节炎症的作用,沙利度胺与甲氨蝶呤有协同作用。

AIM： To investigate the effect of thatlidomide combined with methotrexate on the inflammation and cytokines of rats with collagen type Ⅱ induced arthritis. METHODS： The model of rat was induced by injection of collagen type Ⅱ combined with complete Freund＇ s adjuvant （CFA）. Next day after the injection, the therapeutic administration of thalidomide （ 150mg·kg^-1·d^-1） combined with methotrexate （ 0.2 mg·kg^-1·d^-1） and methotrexate （0.2 mg·kg^-1·d^-1） were differently performed to the rats. The courses of the treatment were all six weeks. The mean arthritis index （AI） was scored every week. The relative concentrations of IL-1β, TNF-α in sera were evaluated by Western Blotting. RESULTS： The therapeutic administration of thalidomide combined with methotrexate and methotrexate could decrease the mean arthritis index on CIA rat, the effect of thalidomide combined with methotrexate was more obvious than that of methotrexate. The administration of thalidomide combined with methotrexate and methotrexate significantly decreased the production of IL-1β and TNF-α, the change of posttreatmentis was obviously in all groups （P 〈 0.05）. CONCLUSION： Thalidomide combined with methotrexate have an inhibitory effect on the expression of IL- 1β and TNF-α in model rat , which is related to its anti-inflammation. There are coordinate effect in thalidomide and methotrexate.