通痹胶囊对佐剂性关节炎大鼠p38MAPK/NF-κB信号通路的影响

Effect of Tongbi capsules on p38MAPK/NF-κB signal pathway in rats with rheumatoid arthritis induced by adjuvant

目的观察通痹胶囊对佐剂性关节炎大鼠血清和滑膜组织中炎性因子表达及p38MAPK/NF-κB信号通路的影响。方法48只Wistar大鼠随机分为正常组、模型组、通痹胶囊不同剂量(375、750、1500mg·kg-1)组及雷公藤多苷片(10 mg·kg^-1)组,除正常组外,其余各组均于右后足跖部注射弗氏完全佐剂造模。造模第8日,各组给予相应药物灌胃治疗,每日1次,连续4周。对大鼠关节炎指数进行监测,足容积法测量致炎侧足肿胀度;灌胃结束后,采用酶联免疫吸附(ELISA)法检测大鼠血清及滑膜中白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的表达水平;蛋白免疫印迹(Western blot)法检测大鼠滑膜组织中p38MAPK、NF-κB/P65、IκBα蛋白表达的。结果与正常组相比,造模后大鼠血清及滑膜组织中IL-1、TNF-α含量明显升高,p38MAPK、NF-κB/P65、IκBα表达显著增多(P<0.01);与模型组相比,通痹胶囊能够有效降低大鼠血清及滑膜组织中IL-1、TNF-α的含量,并抑制滑膜组织中p38MAPK、NF-κB及IκBα的蛋白表达(P<0.05,P<0.01)。结论通痹胶囊具有明显的抗炎作用,其治疗类风湿关节炎的作用机制之一可能为抑制p38MAPK/NF-κB信号通路的激活。

Objective To determine the effect of Tongbi capsules on the expression of inflammatory factors and p38 MAPK/NF-κB signal pathway in rats with arthritis induced by adjuvant.Methods Totally 48 Wistar rats were randomly divided into a nomal group,a model group,3 Tongbi capsule groups at 375,750 and 1500 mg·kg^-1,and a tripterygium glycosides tablet group(10 mg·kg-1).Except for the normal group,the models were established by injecting adjuvant on the right hind paws of the rats.Eight days after modeling,corresponding drugs were given intragastrically,qd,for 4 weeks.The arthritis index of the rats were monitored.Foot volume method was used to determine paw swelling.The interleukin(IL)-1 and tumor necrosis factor(TNF)-αlevel in the serum and synovial tissue of the joint were determined by ELISA;the expressions of p38 MAPK,NF-κB/P65 and IκBαprotein were detected by Western blot.Results Compared with the nomal group,the content of IL-1,TNF-α,and the expressions of p38 MAPK,NF-κB/P65 and IκBαprotein in the serum and synovial tissue of the joint in the model control group were all increased with significant difference(P<0.01).Compared with the model control group,Tongbi capsules effectively reduced the content of IL-1 and TNF-αin the serum and synovial tissue of the joint,and obviously decreased the relative expressions of p38 MAPK,NF-κB and IκBαprotein in the synovial tissues(P<0.05,P<0.01).Conclusion Tongbi capsules show obvious anti-inflammatory effect.One mechanism for rheumatoid arthritis may be to inhibit the activation of p38 MAPK/NF-κB signaling pathway.