沙利度胺及氨甲蝶呤抗CIA大鼠滑膜血管新生及其作用机制的研究

目的研究沙利度胺、氨甲蝶呤对大鼠Ⅱ型胶原诱导型关节炎血管新生的影响及相关的机制。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、甲氨蝶呤和沙利度胺联合甲氨蝶呤治疗,在第6周取膝关节应用免疫组化检测其滑膜的微血管密度(MVD),取血清进行Western Blot检测大鼠体内血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-1、2、3、9的表达并计算相对含量。结果①免疫组织化学染色显示沙利度胺、氨甲蝶呤和沙利度胺联合氨甲蝶呤治疗模型大鼠可使关节滑膜中新生血管数量明显减少.微血管密度(MVD)明显降低(P<0.05).以沙利度胺联合氨甲蝶呤组作用最强。②沙利度胺、氨甲蝶呤和沙利度胺联合氨甲蝶呤可抑制VEGF、MMP-1、2、3、9表达(P均<0.05)。结论沙利度胺和氨甲蝶呤可能通过抑制VEGF,MMP-1、2、3、9的表达而发挥抗滑膜血管新生的作用,且两者有协同作用。

Effect of antiangiogenesis of thalidomide and methotrexate on rats with collagen type Ⅱ induced arthritis

Objective To investigate the effect of thalidomide (THD) and methotrexate (MTX) on rats with collagen typeⅡinduced arthritis,and explore the mechanism of inhibiting an- giogenesis on model rats.Methods The model of rat was induced by injection of collagen typeⅡcombined with complete Freund's adjuvant (CFA).Next day after the injection,the therapeutic administration of thalidomide,methotrexate and thalidomide combined with methotrexate were dif- ferently performed to the rats.Knee joints from the rats sacrificed at the sixth week were estimated in morphology,and the microvessel density (MVD) of synovial membrane was detected using im- munohistochemistry assay.The relative concentration of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1,2,3,9 in sera were evaluated by Western Blotting.Results①The therapeutic administration of THD and MTX or THD+MTX can inhibite antiangiogenesis and decrease the microvessel density (MVD) of synovial membrane on CIA rat.There were more obvi- rous effect in THD+MTX group.②The administration of THD and MTX or THD+MTX signifi- cantly decreased the expression of VEGF、MMP-1,2,3,9 in sera of CIA rat.Conclusions THD and MTX had an inhibitory effect on the expression of VEGF、MMP-1,2,3,9 in model rat, which was related to its antiangiogenesis.There were the Synergetic effect on THD and MTX.