中药干预缺氧诱导因子信号通路治疗骨关节炎研究进展OA

Objective To provide a theoretical basis for the development of new therapeutic targets for osteoarthritis(OA).Methods By retrieving relevant domestic and international literature,the mechanisms of action of the hypoxia-inducible factor(HIF)signaling pathway in the pathological process of OA were summarized.The cartilage-protective functions of HIF-1α(energy metabolism regulation,autophagy activation,extracellular matrix homeostasis maintenance,and anti-apoptotic effects)and the cartilage-destructive mechanisms of HIF-2α(catabolism induction,inflammatory amplification,and promotion of cell death)were analyzed with emphasis.Studies on the regulation of the HIF pathway by traditional Chinese medicine(TCM)monomers and formulas in OA intervention were reviewed,and their targets,signaling networks,and biological effects were summarized.Results HIF-1α maintains chondrocyte energy homeostasis and survival by regulating key glycolytic enzymes,mitochondrial functional factors,and autophagy-related molecules;meanwhile it directly activates the expression of cartilage matrix genes and inhibits Wnt/β-catenin pathway-mediated matrix degradation.HIF-2α drives cartilage destruction by up-regulating pro-inflammatory and matrix-degrading factors,and forms a positive feedback loop with nuclear factor κB(NF-κB)to amplify inflammation.TCM monomers can promote cartilage anabolism by activating the HIF-1α/sex-determining region Y box protein 9(SOX9)axis(such as icariin,baicalin),and alleviate inflammation and matrix degradation by inhibiting the NF-κB/HIF-2α axis(such as curcumin,wogonoside,corylin).TCM formulas(such as Yanghe Decoction,Wenjing Tongluo Decoction,Panalongqi Tablets)can synergistically regulate the balance between HIF-1α and HIF-2α through multiple targets,improve oxidative stress and energy metabolism disorders in the cartilage microenvironment,thereby delaying OA progression.Conclusion TCM exerts cartilage-protective and anti-inflammatory effects by regulating the activity balance between HIF-1α and HIF-2α in the HIF signaling pathway through multiple approaches,reflecting the synergistic advantage of ″multi-component,multi-target,multi-pathway″.