The Research Of "Layers Adjusting External Application" Treating Synovial Inflammation In Knee Osteoarthritis Based On NLRP3/Caspase-1 Inflammasome

Objective:Explore whether the NLRP3/Capase-1 axis is one of the mechanisms in the inflammation in KOA,by which the "Layers Adjusting External Application" can reduce the synovial inflammation in KOA.Method:1.Compare KOA-rats with HE-stained sections of knee joint synovial tissue before and after application of "Layers Adjusting External Application" and normal rats,and calculate the Krenn grade score,and the protein and mRNA expression of inflammatory factors IL-1? and TNF-?;2.Compare the expression levels of NLRP3,pro-caspase-1,and caspase-1 proteins and mRNA in the synovial tissue of knee joints of KOA rats before and after the application of "Layers Adjusting External Application" and after the application of caspase-1 inhibitor3.Observe the change of protein and mRNA expression of MMP-1 and MMP-13 in knee joint cartilage of KOA rats after application of "Layers Adjusting External Application "1 and caspase-1 inhibitor.Result:1.The Krenn grade of synovial tissue in KOA rats was severe synovitis,and the protein and mRNA expression of IL-1? and TNF-?-in the tissues were significantly up-regulated compared to normal synovial tissue,the difference was statistically significant(P?0.05).After application of the "Layers Adjusting External Application",the Krenn grade became mild synovitis,while IL-1?,TNF-a down-regulated significantly,the difference was statistically significant(P<0.05);compare the Yiceng group and the inhibitor group,there was no significant difference in IL-1?,TNF-a expression levels(P>0.05).2.After applying the " Layers Adjusting External Application",the expression levels of NLRP3,caspase-1 and pro-caspase-1 protein and mRNA in synovial tissue of KOA rats were significantly lower than those in KOA group,and the difference was statistically significant(P<0.05);After the application of caspase-1 inhibitor,NLRP3,caspase-1,and ASC were down-regulated compared with KOA group(P<0.05);compare the Yiceng group and the inhibitor group,there was no significant difference in NLRP3,caspase-1 and ASC expression levels(P?0.05).3.The expression of MMP-1 and MMP-13 protein and mRNA in cartilage tissue of KOA rats was decreased after intervention with the "Layers Adjusting External Application ".The difference was statistically significant(P<0.05).Conclusion:The occurrence of synovial inflammation in KOA is closely related to the NLRP3/Caspase-1 axis,and the "Layers Adjusting External Application " has anti-inflammatory effects similar to caspase-1 inhibitors.1."Layers Adjusting External Application" may inhibit KOA synovial inflammation through the down-regulation of NLRP3,ASC and caspase-1 expression to play a therapeutic role.2.The application of the inhibitor of caspase-1 may play a role in the protection of cartilage by reducing the severity of synovial inflammation,"Layers Adjusting External Application" has similar acivity.