Abstract:Objective:To investigate the effect of Huangqi Guizhi Wuwu tang on cartilage injury and nucleotide- binding oligomerization domain- like receptor 3(NLRP3)/aspartic acid protease 1(Caspase1) pathway in rats with knee osteoarthritis (KOA). Methods: A total of 120 SD rats were randomly divided into the control group, the model group, the meloxicam group and the Huangqi Guizhi Wuwu tang groups of low- dose,medium- dose and high- dose. Except those in the control group, rat models of cartilage injury in KOA were established in all the other groups. After successful establishment, the control group and the model group were given the same volume of saline;the meloxicam group was given 40.0 mg/kg of meloxicam solution;the Huangqi Guizhi Wuwu tang groups of low-dose,medium-dose and high-dose were respectively given 20.0, 40.0 and 80.0 mg/kg of Huangqi Guizhi Wuwu tang. After experiment, the scores of joint inflammation and Mankin's scores of cartilage in rats with KOA were performed, and paw withdrawal pressure threshold(PWPT) and paw withdrawal thermal latency(PWTL) were measured; mRNA and protein expression levels of NLRP3 and Caspase1 and the expression levels of interleukin- 1β(IL- 1β),interleukin- 6(IL- 6) and tumor necrosis factor- α(TNF- α) in knee joint cartilage were measured. Results: Compared with those in the control group, the PWPT and PWTL in the model group were decreased(P<0.05);the scores of joint inflammation,Mankin's scores,mRNA and protein expression levels of NLRP3 and Caspase1,and protein expression levels of IL- 1β,IL-6 and TNF-α were increased(P<0.05). Compared with those in the model group, the PWPT and PWTL in the meloxicam group and the Huangqi Guizhi Wuwu tang groups of all doses were increased(P<0.05);the scores of joint inflammation,Mankin's scores,mRNA and protein expression levels of NLRP3 and Caspase1,and protein expression levels of IL-1β,IL-6 and TNF-α were decreased(P<0.05),and there was a significant dose-effect relationship being found in the Huangqi Guizhi Wuwu tang groups of all doses(P<0.05). Compared with those in the meloxicam group,the PWPT and PWTL in the Huangqi Guizhi Wuwu tang groups of low-dose and medium-dose were lower(P<0.05); the scores of joint inflammation, Mankin's scores, mRNA and protein expression levels of NLRP3 and Caspase1, and protein expression levels of IL- 1β, IL- 6 and TNF- α were higher(P<0.05); there was no significant difference being found in the comparison of the above indexes in the Huangqi Guizhi Wuwu tang groups of high- dose(P> 0.05). Conclusion:The application of Huangqi Guizhi Wuwu tang can reduce the degree of cartilage injury in KOA,especially in high dose. Its mechanism is related to the fact that Huangqi Guizhi Wuwu tang can reduce the mRNA and protein expression of the inflammatory signaling pathways of NLRP3 and Caspase1 and thus inhibiting the expression of inflammatory factors including IL-1β,IL-6 and TNF-α.