中药药理与临床2025，Vol.41Issue(5)：27-33,7.
青藤碱通过JAK/STAT通路调控巨噬细胞极化改善胶原诱导性关节炎大鼠炎症和骨破坏的作用研究
Sinomenine Ameliorates Inflammation and Bone Destruction in Rat Model of Collagen-Induced Arthritis by Regulating Macrophage Polarization via JAK/STAT Pathway
摘要
Abstract
Objective:To investigate the regulatory effects of sinomenine on macrophage polarization in the rat model of collagen-induced arthritis(CIA)and delve into the underlying mechanisms,with a particular focus on the Janus kinase(JAK)/signal transducer and activator of tran-scription(STAT)signaling pathway.Methods:Forty-eight Wistar female rats were randomized into normal control,model control,tofacitinib(0.002 g/kg),sinomenine(0.04,0.16 g/kg),and sinomenine+tofacitinib(0.16 g/kg sinomenine+0.002 g/kg tofacitinib)groups.Ex-cept the normal control group,other groups were modeled for CIA.After successful modeling,rats in the treatment groups were administrated with corresponding drugs by gavage,once daily for 28 days.The arthritis index and the degree of paw swelling were observed and recorded.Histopathological changes in the ankle joints were assessed by hematoxylin-eosin staining.Bone mineral density(BMD),bone volume fraction(BV/TV),bone surface area-to-bone volume ratio(BS/BV),and trabecular separation(Tb.Sp)were measured by micro-computed tomo-graphy.Additionally,the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-4,and IL-10 in the rat serum were determined by enzyme-linked immunosorbent assay.The expression of macrophage markers CD86 and CD206 in the synovial membrane of ankle joints was evaluated by immunohistochemistry(IHC).Western blotting was performed to assess the protein levels of CD86,CD206,phosphorylated(p)-JAK1,JAK1,p-STAT3,and STAT3 in the synovial membrane of ankle joints.Results:Compared with the normal control group,the mod-el control group exhibited significantly increased arthritis index and degree of paw swelling,narrowed ankle joint space,abnormal synovial tis-sue proliferation,severe destruction of articular cartilage and bone,decreased BMD and BV/TV,and increased BS/BV and Tb.Sp.Further-more,the expression of the M1 macrophage marker CD86 in the synovial membrane of ankle joints and the levels of pro-inflammatory cytokines TNF-α and IL-6 in the serum elevated,while the expression of the M2 macrophage marker CD206 and the levels of anti-inflammatory cyto-kines IL-4 and IL-10 in serum decreased in the model control group.Additionally,the ratios of p-JAK1/JAK1 and p-STAT3/STAT3 in the synovial membrane of ankle joints increased(P<0.01).Compared with the model control group,all the drug treatment groups showed signifi-cantly reduced arthritis index and degree of paw swelling,alleviated histopathological changes in the ankle joints and destruction of articular cartilage and bone,reduced expression of CD86 in the synovial membrane of ankle joints and levels of TNF-α and IL-6 in the serum were de-creased,and increased expression of CD206 and levels of IL-4 and IL-10 in the serum.Moreover,the ratios of p-JAK1/JAK1 and p-STAT3/STAT3 in the synovial membrane of ankle joints declined in the treatment groups(P<0.05 or P<0.01).The sinomenine+tofacitinib group exhibited the best therapeutic effect.Conclusion:Sinomenine can inhibit macrophage polarization towards the M1 phenotype and induce po-larization towards the M2 phenotype,thereby restoring the M1/M2 balance,reducing inflammatory cytokine levels,and effectively alleviating joint inflammation and bone destruction in CIA rats.This mechanism of action may be related to the JAK/STAT signaling pathway.关键词
青藤碱/胶原诱导性关节炎/巨噬细胞极化/炎症/骨破坏/酪氨酸激酶/信号转导与转录激活因子信号通路Key words
Sinomenine/Collagen-induced arthritis/Macrophage polarization/Inflammation/Bone destruction/Janus kinase/signal transducer and activator of transcription signaling pathway引用本文复制引用
王金凤,王枫,刘杰,刘晓庆,马腾茂,刘咏梅..青藤碱通过JAK/STAT通路调控巨噬细胞极化改善胶原诱导性关节炎大鼠炎症和骨破坏的作用研究[J].中药药理与临床,2025,41(5):27-33,7.基金项目
山东省中医药科技重点项目(编号:Z-2023079) （编号:Z-2023079）
山东省医药卫生科技发展计划项目(编号:202202070893) （编号:202202070893）
山东省医药卫生科技项目(编号:202302041492). （编号:202302041492）
