基于NLRP3信号通路探讨三痹汤对佐剂型关节炎大鼠的治疗作用及机制探讨OA

Objective:To investigate the effect of Sanbi Decoction(SBD)on adjuvant arthritis(AA)rats and NLRP3 signaling pathway.Methods:Sixty Wistar rats were randomly divided into control group,model group,leflunomide group,and SBD high dose(SBD-H),SBD medium dose(SBD-M),and SBD low dose(SBD-L)groups,with 10 rats in each group.Rat AA model was prepared by Freund's complete adjuvant,and corresponding drugs were administered orally to each group one week after the initial immunization.After continuous drug administration for 21 days,the rats were euthanize on 28 days after immunization.The general state,volume of foot,arthritis index(AI)and histopathologic morphology of ankle synovium were observed.The contents of IL-1β and IL-18 were detected by ELISA,and the expression levels of NLRP3 mRNA,NLRP3 and Caspase-1 protein were detected by PCR and immunohistochemistry.Results:Compared with control group,the ankle swelling and pathological injury of model group were serious,and the foot volume was significantly increased from the 7th to 28th days(P＜0.05).The contents of IL-1β and IL-18,the expression levels of NLRP3 mRNA,NLRP3,and Caspase-1 protein were significantly increased(P＜0.05).Compared with model group,the ankle swelling and pathological injury in SBD-H,SBD-M,SBD-L and leflunomide groups were improved to varying degrees,and the foot volume and arthritis index were significantly decreased from day 7 to 28(P＜0.05).The contents of IL-1β and IL-18,and the expression levels of NLRP3 mRNA protein,NLRP3,and Caspase-1 protein were significantly decreased(P＜0.05).The degree of improvement of ankle swelling and pathological injury was SBD-H＞SBD-M＞SBD-L.Compared with SBD-H group,the contents of IL-1β and IL-18 in SBD-L group increased(P＜0.05),NLRP3 mRNA protein expression and NLRP3 and Caspase 1 protein levels in SBD-M and SBD-L groups were significantly increased(P＜0.05).Compared with leflunomide group,the improvement degree of ankle swelling and pathological injury of SBD-H group was basically the same,the contents of IL-1β and IL-18 in SBD-M and SBD-L groups were increased(P＜0.05),while the content difference of IL-1β and IL-18 in SBD-H group were not statistically significant(P＞0.05);the NLRP3 mRNA protein expression level in SBD-L group was significantly increased(P＜0.05),and the NLRP3,Caspase-1 protein expression levels of SBD-M and SBD-L groups were increased(P＜0.05);however,there were no significant difference in NLRP3 and Caspase-1 protein expression levels in SBD-H group(P＞0.05).Conclusion:Sanbi Decoction may reduce the level of IL-1β and IL-18 in serum by inhibiting the activation of NLRP3 signaling pathway,and improve the degree of synovial injury in rats with adjuvant arthritis.