时珍国医国药2026，Vol.37Issue(3)：424-431,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-0304
膝痹宁Ⅱ通过STAT6/PPAR-γ信号通路调节滑膜巨噬细胞极化改善膝骨关节炎的作用机制
The mechanism of Xibining(膝痹宁)Ⅱ in ameliorating knee osteoarthritis through regulation of synovial macrophage polarization via the STAT6/PPAR-γ signaling pathway
摘要
Abstract
Objective To investigate the protective mechanism of Xibining Ⅱ(膝痹宁,XBN)against knee osteoarthritis(KOA)through the modulation of synovial macrophage polarization via the STAT6/PPAR-γ signaling pathway.Methods Forty Sprague-Dawley(SD)rats were randomly assigned to five groups(n=8).Mechanical pain threshold,joint swelling degree,range of motion,and gait scores were evaluated.Histopathological alterations in cartilage and synovial tissues were examined using Toluidine Blue,Safranin O-Fast Green,and Hematoxylin and Eosin(H&E)staining.Synovial macrophage polarization was analyzed by flow cytometry.The con-centrations of IL-6,IL-1β,and TNF-α in serum and synovial fluid were measured using ELISA.The mRNA and protein expression levels of key factors in the STAT6/PPAR-γ pathway within the synovial tissue were determined by quantitative PCR(qPCR)and West-ern blotting,respectively.Results Compared with the Model group,rats treated with low-and high-dose XBN demonstrated significant amelioration of histopathological damage in both cartilage and synovial tissues.Furthermore,these groups exhibited markedly improved joint mobility,an increased proportion of M2 macrophages in the synovium,and elevated expression levels of proteins and mRNAs asso-ciated with the STAT6/PPAR-γ signaling pathway(P<0.05).Conversely,a significant reduction was observed in the joint swelling rate,gait score,OARSI score for cartilage,Krenn score for synovitis,the proportion of M1 macrophages,the M1/M2 ratio,and the levels of IL-6,IL-1β,and TNF-α in both serum and joint fluid(P<0.05).The therapeutic effects of high-dose XBN were consistently more potent than those of the low-dose regimen.Co-administration of the PPAR-γ antagonist GW9662 largely abolished the protective effects of XBN on all the aforementioned indices in KOA rats.Conclusion Xibining II mitigates synovial inflammation and improves clinical symptoms of KOA,including pain,swelling,and functional impairment,by promoting the shift of macrophage polarization from the M1 to the M2 phenotype.This mechanism is likely mediated through the activation of the STAT6/PPAR-γ signaling pathway.关键词
膝痹宁Ⅱ/膝骨关节炎/滑膜/巨噬细胞极化/STAT6/PPAR-γ信号通路Key words
Xibining(膝痹宁)Ⅱ Prescription/Knee osteoarthritis(KOA)/Synovial/Macrophage polarization/STAT6/PPAR-γ signaling pathway分类
医药卫生引用本文复制引用
魏义保,廖太阳,魏楚军,刘德仁,胡恩睿,茆军,王培民..膝痹宁Ⅱ通过STAT6/PPAR-γ信号通路调节滑膜巨噬细胞极化改善膝骨关节炎的作用机制[J].时珍国医国药,2026,37(3):424-431,8.基金项目
国家自然科学基金面上项目(82575102) （82575102）
江苏省医学重点学科/实验室建设单位项目(JSDW202252) （JSDW202252）
江苏省中医院中医膝骨关节炎临床医学创新中心项目(Y2023zx05) （Y2023zx05）
南京中医药大学膝骨关节炎临床专病研究院项目(LCZBYJYZZ2024-003) （LCZBYJYZZ2024-003）
