基于动力蛋白调控NLRP3转运探讨生骨再造丸对激素性股骨头坏死的影响OA

Objective To explore the key links and mechanisms of Shenggu Zaizao Pill(生骨再造丸,SGZZP)in treating steroid-associated necrosis of the femoral head(SANFH),investigate the relationship between SANFH pathogenesis and dynein-mediated NLRP3 inflammasome regulation,and clarify the therapeutic targets of SGZZP,thereby elucidating its pharmacological mechanism.Methods BMSCs were divided into a control group,a dexamethasone(Dex)+lipopolysaccharide(LPS)model group,a model group treated with the dynein inhibitor Dynarrestin,and a model group treated with SGZZP-containing serum.After respective treatments,cells were collected for analysis.Cell viability was assessed using a CCK-8 assay.The apoptosis rate was measured by flow cytometry(FCM).The protein expression levels of Dynein,NLRP3,Caspase-1,and GSDMD were determined by Western blot(WB).The con-centrations of IL-1β and IL-18 in the cell culture supernatant were measured by ELISA.Results Compared with the control group,the Dex+LPS model group exhibited decreased cell viability and increased apoptosis.The protein expression of Dynein,NLRP3,Caspase-1,and GSDMD was significantly up-regulated(P<0.0001).as well as the concentrations of IL-1β and IL-18,were markedly elevated(P<0.0001).In contrast,both Dynarrestin and SGZZP-containing serum treatment increased cell viability and reduced apoptosis com-pared to the model group.GSDMD and the concentrations of IL-1β and IL-18(P<0.0001).Conclusion SGZZP inhibits Dynein-mediated microtubule-dependent transport of NLRP3,which subsequently suppresses NLRP3 inflammasome assembly and effectively alleviates BMSCs pyroptosis.