Mitigation Effect of Xibining on Synovitis of Knee Osteoarthritis Based on the Activation of NLRP3 Inflammasomes in Hypoxic Tissues

OBJECTIVE To explore the mitigation effect of Xibining on synovitis of knee osteoarthritis baesd on the activation of NLRP3 inflammasomes in hypoxic tissues. METHODS The rats were divided into three groups: normal group， KOA group and Xibining group. Xibining group was gavaged with drug liquid while the normal group and KOA group were treated with the same amount of sterilized saline as control. On the 56th day， the rats were killed to obtain synovial tissue. HE staining was performed to evaluate synovial inflammation and Hypoxyprobe hypoxia probe immunofluorescence staining was used to observe the degree of hypoxia in the synovial tissue of rats. qPCR and Western blot were performed to detect both gene and protein expression of HIF-1α， NLRP3， Caspase-1 p10 and GSDMD， respectively. The contents of IL-1β and IL-18， which were downstream from the activation of NLRP3 inflammasomes， were determined by ELISA. RESULTS Immunofluorescence staining with hypoxyprobe probe showed that the degree of hypoxia in synovial tissue of KOA rats was more severe than that of normal rats， and Xibining group was less than KOA. In HE staining， the synovial tissue of the KOA group showed more inflammatory cell infiltration and the lining layer cells were more disarranged than that of the normal group. The infiltration of inflammatory cells in the Xibining group was less than that in the KOA group. Meanwhile， both mRNA and protein level of HIF-1α in KOA group were higher than those in normal group (P<0.01)， and Xibining group were lower than those in KOA group (P<0.01). In addition， both mRNA and protein expression of Caspase-1 p10， NLRP3 and GSDMD in KOA group were higher than those in normal group (P<0.05)， while those in Xibining group were lower than those in KOA group (P<0.05). The contents of IL-1β and IL-18 in synovial tissue of KOA group was higher than that of normal group (P<0.01)， and that of Xibining group was lower than that of KOA group (P<0.01). CONCLUSION Xibining can effectively improve the condition of hypoxia in synovial tissue of KOA， down-regulate the expression of HIF-1α， decrease the activation of NLRP3 inflammasomes， and alleviate synovitis.