上中下通用痛风方对痛风性关节炎大鼠NLRP3/Caspase-1/IL-1β信号通路的影响OA

Objective:To explore the effect of Shangzhongxia Tongyong Gout Formula(STGF)on NLRP3/Caspase-1/IL-1β signaling pathway in rats with gouty arthritis(GA)induced by sodium urate.Methods:Fifty-six SD male rats were randomly divided into a blank group,a model group,a colchicine group,a gout relieving group,and a low,medium,and high STGF groups.The blank group and model group were gavaged physiological saline,the colchicine group and gout relief group were gavaged colchicine suspension(0.5 mg/kg)and gout relief suspension(375 mg/kg),while the low,medium,and high-dose STGF groups were gavaged STGF(5,10,and 15 g/kg).An hour after last administration,the blank group was injected with 0.2 mL of physiological saline into the left joint cavity of the rats,while the rats in the other 6 groups were all injected with 3%potassium oxyzinate suspension solution into the abdominal cavity.Sodium urate suspension 0.2 mL was injected into the left knee joint cavity to prepare a GA rat model.The contents of IL-1β and TNF-α in serum of rats were detected by ELISA.The protein levels of NLRP3 and cleaved Caspase-1 in synovial tissues were detected by Western blot.Results:Serum levels of IL-1β and TNF-α in model group were higher than those in blank group(P<0.05).Compared with model group,the contents of IL-1β and TNF-α in serum of rats in low,medium and high dose STGF groups,colchicine group and gout relieving group decreased(P<0.05).Compared with colchicine group and gout relieving group,the IL-1β content of STGF low and medium dose groups increased(P<0.05),the IL-1β content of STGF high dose group had no significant difference(P>0.05),and the TNF-α content of STGF low,middle and high dose groups increased(P<0.05).The contents of IL-1β and TNF-α in high-dose STGF group decreased compared with those in low-dose STGF group(P<0.05).The expression of NLRP3 and cleaved Caspase-1 protein in synovial tissue of rats in the model group was up-regulated compared with that in the blank group(P<0.05).Compared with model group,NLRP3 and cleaved Caspase-1 protein expression were down-regulated in STGF medium and high dose groups(P<0.05),and there were no significant differences in NLRP3 and cleaved Caspase-1 protein expression in STGF low dose group(P>0.05).Compared with colchicine group,NLRP3 protein expression was up-regulated in low-dose STGF group(P<0.05),but there was no significant difference in NLRP3 protein expression of medium and high-dose STGF groups(P>0.05).Compared with gout relieving group,there were no significant differences in cleaved Caspase-1 protein expression in synovial tissue in low,medium,and high dose STGF groups(P>0.05).Conclusion:STGF medium and high dose groups can significantly reduce GA inflammatory factors,and up-regulated NLRP3 and cleaved Caspase-1 protein expression,which may be related to the NLRP3/Caspase-1/IL-1β signaling pathway.