雷公藤多苷调节胆碱能抗炎通路改善胶原诱导性关节炎

Improvement Effect of Tripterygium Glycosides on Collagen-induced Arthritis by Regulating Cholinergic Anti-inflammatory Pathway

目的:探索雷公藤多苷对胶原诱导性关节炎大鼠胆碱能抗炎通路及关节损伤的影响。方法:Wistar大鼠随机分为正常对照组、模型组、激动剂组、抑制剂组、甲氨蝶呤组、雷公藤多苷组、益肾蠲痹丸组。除正常对照组外其余各组均用Ⅱ型胶原和完全弗氏佐剂制备类风湿关节炎模型,分别用生理盐水、PNU-282987、α-银环蛇毒素、甲氨蝶呤、雷公藤多苷、益肾蠲痹丸等药物进行干预。HE染色观察大鼠关节损伤情况,检测大鼠α7烟碱型乙酰胆碱能受体(α7nAChR)表达,并评估大鼠NF-κB及JAK2/STAT3通路活性(检测NF-κB p65、磷酸化NF-κB p65、磷酸化NF-κB p65 DNA结合活性、JAK2、STAT3、磷酸化STAT3、TNF-α、IL-6、IL-17、HMGB1的水平)。结果:与正常对照组比较,模型组及抑制剂组大鼠关节存在明显病理损伤,α7nAChR蛋白表达显著降低(P<0.05),NF-κB及JAK2/STAT3通路过度激活(P<0.05)。与模型组比较,雷公藤多苷组大鼠关节破坏减轻,α7nAChR蛋白表达显著增加(P<0.05),NF-κB及JAK2/STAT3通路活性显著降低(P<0.05)。结论:雷公藤多苷可调节胶原诱导性关节炎大鼠胆碱能抗炎通路,改善其关节损伤。

Objective:To explore the effects of tripterysium glycosides on cholinergic anti-inflammatory pathways and joint injury in collagen-induced arthritis rats.Methods:The Wistar rats were randomly divided into normal control group,model group,agonist group,antagonist group,methotrexate group,tripterysium glycosides group,Yishen juanbi pills group.Except the normal control group,other groups were given collagen typeⅡand complete freund′s adjuvant to prepare rheumatoid arthritis model,respectively,the normal saline,PNU-282987,α-bungarotoxin,methotrexate,tripterysium glycosides,Yishen juanbi pills and other drugs were used for intervention.Joint injuries of rats were observed by HE staining,the expression ofα7 nicotinic acetylcholinergic receptor(α7 nAChR)in rats was detected,the activities of NF-κB and JAK2/STAT3 pathways in rats were evaluated.The levels of NF-κB p65,phosphorylated NF-κB p65,phosphorylated NF-κB p65 DNA binding activity,JAK2,STAT3,phosphorylated STAT3,TNF-α,IL-6,IL-17 and HMGB1 were detected.Results:Compared with the normal control group,the joints were pathologically damaged in the model group and antagonist group rats,the expression ofα7 nAChR protein was significantly reduced(P<0.05)and the NF-κB and JAK2/STAT3 pathways were over-activated(P<0.05).Compared with model group,the joint damage in tripterysium glycosides group rats was reduced,the expression ofα7 nAChR protein was significantly increased(P<0.05),and the NF-κB and JAK2/STAT3 pathway activities were significantly decreased(P<0.05).Conclusion:Tripterysium glycosides can improve the arthritic damage by regulating of choline anti-inflammatory pathways in collagen-induced arthritis rats.