| Objective To explore the mechanism of the effect of Chonggu granules on pyroptosis in rats with the knee osteoarthritis (KOA) through the NLRP3/Caspase-1/GSDMD pathway. Methods Thirty-two SPF SD rats were randomly assigned to four groups: Chonggu granule, model, blank, and positive control. Each group consisted of eight rats. Except for rats in the blank group, rats in other groups received injection of papain solution into the joint cavity under anesthesia for one week to achieve knee osteoarthritis model. Rats in each group received treatment for four weeks following the successful modeling. Under an electron microscope, the burned-out knee cartilage cells were examined. ELISA was used to measure the serum levels of IL-18, IL-17, IL-6, and IL-1β. Using immunofluorescence, the expressions of NLRP3, caspase-1, GSDMD, and ASC were quantified in the cartilage tissues of rats. Using qRT-PCR, the mRNA expression levels of GSDMD, caspase-1, and NLRP3 were examined. Results Compared to the model group, Chonggu granules were able to prevent pathological cartilage tissue damage and to decrease the serum expressions of IL-1β, IL-18, IL-6, and IL-17 in rats (P<0.05). They also reduced the mRNA and protein expressions of GSDMD, Caspase-1, NLRP3 (P<0.05). Conclusion In KOA rats, articular cartilage damage can be improved with Chonggu granules, which also decrease the degree of apoptosis and the production of inflammatory markers. The mechanism behind these effects may be connected to the modulation of the NLRP3/Caspase-1/GSDMD signaling pathway, which lowers cell death. |