Experimental Study of Bushen Qiangjin Capsule onImproving KOA Synovitis and Fibrosis by Regulating NLRP3 Inflammasome-Mediated Pyroptosis
- VernacularTitle:补肾强筋胶囊通过调控NLRP3炎症小体介导的细胞焦亡改善KOA滑膜炎症和纤维化的实验研究
- Author:
Yi WANG
1
,
2
;
Tao JIANG
;
Wengang LIU
;
Xuemeng XU
Author Information
- Keywords: Bushen Qiangjin capsule; Knee osteoarthritis; NLRP3 Inflammasome; Pyroptosis; Synovial fibrosis; Experimental study
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1471-1480
- CountryChina
- Language:Chinese
- Abstract: Objective To explore the possible mechanism of Bushen Qiangjin capsule on synovitis and fibrosis in knee osteoarthritis(KOA).Methods In the animal experiment,the animal model of KOA was established by anterior cruciate ligament transection(ACLT).The rats were randomly divided into blank group,model group,Bushen Qiangjin capsule group and celecoxib capsule group.The levels of interleukin-1β(IL-1β)and IL-18 in serum of rats in each group were detected by ELISA,and the histopathological changes of synovium of rats in each group were observed by HE and Sirius red staining.Immunohistochemical staining was used to observe the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 in synovium of rats in each group.In the cell experiment,Lipopolysaccharide(LPS)combined with Adenosine triphosphate(ATP)was used to stimulate rat-FLS to simulate OA inflammatory environment and induce pyroptosis model.The cells were treated with Bushen Qiangjin capsule or MCC950,and the levels of IL-1β and IL-18 in the cell culture supernatant of each group were detected by ELISA;the localization and expression of NLRP3,Caspase-1 and GSDMD were observed by immunofluorescence staining;and the mRNA and protein expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2 and TIMP1 were detected by RT-qPCR and Western Blot,respectively.Results The results of animal experiment showed that compared with the model group,Bushen Qiangjin capsule could significantly reduce the score of synovial histomorphology of KOA rats(P<0.01);significantly reduce the levels of IL-1β and IL-18 in serum of KOA rats(P<0.01);also reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 protein in synovium of KOA rats(P<0.05,P<0.01).The results of cell experiment showed that compared with the model control group,Bushen Qiangjin capsule could significantly reduce the levels of IL-1β and IL-18 in the supernatant of cell culture(P<0.01);significantly reduce the relative fluorescence expression of NLRP3,Caspase-1 and GSDMD(P<0.01),and significantly reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2,TIMP1 mRNA and protein(P<0.01).Conclusion Bushen Qiangjin capsule could improve KOA synovitis and fibrosis by inhibiting the activation of NLRP3 inflammasome and regulating FLS pyroptosis.
