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OA
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
目的 基于STAT6/PPAR-γ信号通路探讨膝痹宁Ⅱ(XBN)调节滑膜巨噬细胞极化改善膝骨关节炎(KOA)的保护机制.方法 40只SD大鼠随机均分为5组.检测各组大鼠关节压痛阈值、关节肿胀率、关节活动度与步态评分;甲苯胺蓝、番红O-固绿染色和HE染色分别检测各组大鼠软骨与滑膜组织病理形态;流式细胞术检测各组大鼠滑膜组织巨噬细胞极化情况;ELISA检测各组大鼠血清与关节液中IL-6、IL-1β、TNF-α水平;qPCR和Western blot检测各组大鼠关节滑膜组织STAT6/PPAR-γ通路相关蛋白和mRNA表达水平.结果 与Model组比较,XBN低、高剂量组大鼠软骨与滑膜组织病理形态均明显改善,关节活动度、滑膜组织中M2型巨噬细胞占比、STAT6/PPAR-γ信号通路相关蛋白和mRNA表达水平均明显升高(P<0.05);关节肿胀率、步态评分、软骨OARSI评分、滑膜炎Krenn评分、滑膜组织M1型巨噬细胞占比与M1/M2比值、血清与关节液中IL-6、IL-1β和TNF-α水平均明显降低(P<0.05),且高剂量XBN的作用更强;GW9662可明显减弱XBN对KOA大鼠上述各指标的作用.结论 膝痹宁Ⅱ可通过激活STAT6/PPAR-γ信号通路促使M1型巨噬细胞向M2型极化,减轻KOA大鼠滑膜炎症,改善KOA关节疼痛、肿胀、活动功能减退等症状.
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.
魏义保;廖太阳;魏楚军;刘德仁;胡恩睿;茆军;王培民
南京中医药大学附属医院,江苏 南京 210029南京中医药大学第二附属医院,江苏 南京 210017大连医科大学研究生院,辽宁 大连 116044南京中医药大学附属医院,江苏 南京 210029南京中医药大学附属医院,江苏 南京 210029南京中医药大学附属医院,江苏 南京 210029南京中医药大学附属医院,江苏 南京 210029
医药卫生
膝痹宁Ⅱ膝骨关节炎滑膜巨噬细胞极化STAT6/PPAR-γ信号通路
Xibining(膝痹宁)Ⅱ PrescriptionKnee osteoarthritis(KOA)SynovialMacrophage polarizationSTAT6/PPAR-γ signaling pathway
《时珍国医国药》 2026 (3)
424-431,8
国家自然科学基金面上项目(82575102)江苏省医学重点学科/实验室建设单位项目(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)南京中医药大学膝骨关节炎临床专病研究院项目(LCZBYJYZZ2024-003)
评论