肿瘤坏死因子受体-抗体融合蛋白对佐剂性关节炎大鼠滑膜中TNF-α、TGF-β1和VEGF表达的影响

Effect of rhu-TNFR-Fc on the expression of TNF-α,TGF-β1 and VEGF in synovium of rats with adjuvant arthritis

目的探讨肿瘤坏死因子受体-抗体融合蛋白对佐剂性关节炎大鼠滑膜中肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)血管内皮生长因子(VEGF)表达的影响。方法将成年雄性Wistar大鼠随机分为5组,Ⅱ～Ⅴ组建立佐剂性关节炎大鼠(AA)模型,于造模后第12天开始Ⅲ组给予甲氨喋呤灌胃治疗,Ⅳ～Ⅴ组给予益赛普皮下注射治疗。第28天取膝关节滑膜,常规HE染色,计算滑膜病理积分,免疫组织化学染色检测TNF-α、TGF-β1和VEGF在膝关节滑膜的表达。结果正常对照组大鼠滑膜组织均有少量TNF-α、TGF-β1和VEGF的表达,Ⅱ～Ⅴ组较Ⅰ组均明显增高(P<0.05)。Ⅳ、Ⅴ组滑膜组织TNF-α表达较Ⅱ组明显减低(P<0.05),而Ⅲ组与Ⅱ组无统计学意义(P>0.05)。Ⅲ～Ⅴ组滑膜组织TGF-β1、VEGF的表达均明显低于Ⅱ组,差异有统计学意义(P<0.05)。结论可溶性重组人肿瘤坏死因子受体-抗体融合蛋白可明显降低AA大鼠滑膜组织TNF-α、TGF-β1和VEGF表达,对AA大鼠的关节炎症有明显的治疗作用,可能抑制局部组织血管新生。

Objective To investigate the effect of rhu-TNFR-Fc （etanercept） on the expression of TNF-α, TGF-β1 and VEGF in synovium of rats with adjuvant arthritis （AA）. Methods The adult male Wistar rats were randomly divided into 5 groups： the rats in group Ⅱ～Ⅴ were injected with Freund complete adjuvant to induce the experimental animal models with AA,on the 12th day after induction,the rats in group m were given MTX （2.7mg/kg. w） by gavage;the rats in groupiv and group V were given etanercept by subcutaneous injection. After 28 days, the synovium of joint of rats was taken out to be HE stained,then synovium pathological score was calculated, and the expression levels of TNF-α, TGF-β1 and VEGF protein in synovium of knee joint were detected by histoimmunochemistry, Results The expression levels of TNF-α,TGF-β1 and VEGF in group Ⅱ～Ⅴ were significantly higher than those in group I （ P 〈 0.05 ） , The expression levels of TNF-α in group Ⅳ and group V were obviously decreased, as compared with those in group Ⅱ （ P 〈 0.05 ）, however, there were no significant differences between group m and group Ⅱ （ P 〉 0.05 ）. The expression levels of TGF-β1 and VEGF in rats＇synovium tissues in group Ⅲ～Ⅴ were significantly lower than those in group Ⅱ （ P 〈 0. 05 ）. Conclusion Etanercept can obviously reduce the expression levels of TNF-α, TGF-β1 and VEGF in rats＇ synovium tissues, which has obvious therapeutic effect on joint inflammation of rats with AA. which may inhibit blood vessel neogenesis in local tissues.