异绿原酸A抑制NLRP3炎性复合体/NF-κB活化减轻胶原诱导型关节炎大鼠炎症反应

Isochlorogenic acid A inhibits activation of NLRP3/NF-κB in rats with collagen-induced arthritis

目的分析异绿原酸A对胶原诱导型关节炎大鼠抗炎效应与潜在作用机制。方法SD♂大鼠分为正常组、模型组、异绿原酸A高、低剂量组。高、低剂量异绿原酸A连续给药6周,测量大鼠足跖肿胀度,脾脏脏器系数;HE染色观察骨关节病理改变;Westernblot检测关节滑膜NLRP3、caspase-1、NF-κBp65、p-NF-κBp65、p-IκB-ɑ、RANKL蛋白表达;ELISA检测血浆IL-1β、IL-6、TNF-ɑ、CRP、IFN-γ、IL-18表达。结果与正常组比较,模型组大鼠足跖明显肿胀,脾脏系数变大;关节滑膜内NLRP3、caspase-1、NF-κBp65、p-NF-κBp65、p-IκB、RANKL蛋白表达明显升高;血浆IL-1β、IL-6、TNF-ɑ、CRP、IFN-γ、IL-18明显上升。不同剂量异绿原酸A能明显降低模型组上述各项指标。结论异绿原酸A对胶原诱导型关节炎有较好的抗炎作用,其抗炎活性可能与降低NLRP3炎性复合体激活和NF-κB磷酸化表达有关。

Aim To analyse the anti-inflammatory effect of isochlorogenic acid A in rats with collagen-induced arthritis and the potential mechanism.Methods Male SD rats were randomly divided into normal group,model group,isochlorogenic acid A high and low dose groups.The model was constructed in all groups except control group.After continuous administration for six weeks,the plantar thickness and spleen organ coefficient were measured in rats.NLRP3,caspase-1,NF-κB p65,p-NF-κB p65,p-IκB and RANKL protein in synovium of joint were detected by Western blot,and IL-1β,IL-6,TNF-ɑ,CRP,IFN-γ,IL-18 expressions in blood plasma were detected by ELISA kit.Results Compared with normal group,the swelling degree of plantar and the spleen organ coefficient in model group increased significantly.Western blot showed that the expression of NLRP3,caspase-1,NF-κB p65,p-NF-κB p65,p-IκB-ɑ and RANKL protein were up-regulated in synovium of joint tissues in model group.ELISA showed that the expression of blood plasma IL-1β,IL-6,TNF-ɑ,CRP,IFN-γ and IL-18 were significantly up-regulated in model group.Different doses of isochlorogenic acid A can significantly reduce the performance of the above indicators in model group.Conclusions Isochlorogenic acid A has a good anti-inflammatory effect on collagen-induced arthritis,and its anti-inflammatory activity may be related to the decrease of NLRP3 inflammatory complex activation and NF-κB phosphorylation.