基于异常机械应力探讨中医药调控髓核细胞铁死亡防治椎间盘退变的研究进展OA

The progressive reduction in the number of nucleus pulposus cells(NPCs)is a central pathological event in the onset and progression of intervertebral disc degeneration(IVDD).Aberrant mechanical stress may accelerate the progression of IVDD by triggering ferroptosis in NPCs via the mechanosensitive ion channel Piezo1,thereby inducing concurrent dysregulation of iron metab-olism and mitochondrial damage.Therefore,elucidating the mechanisms by which Traditional Chinese Medicine(TCM)modulates NPC ferroptosis has become an emerging focus in IVDD research.Emerging evidence suggests that classical TCM formulas,such as Liuwei Dihuang Pill,Fuzi Decoction,Duhuo Jisheng Decoction,and Shentong Zhuyu Decoction,bioactive compounds,such as hinok-itiol,hesperidin,gallic acid,cynarin,and icariin,and external therapies,like acupuncture and electroacupuncture,may modulate Piezo1-mediated mechanical-biological transduction.Mechanistically,these interventions may the expression of upregulate ferropor-tin(FPN)and metal-regulatory transcription factor 1(MTF1)to restore cellular iron homeostasis,suppress the production of reactive oxygen species(ROS),and help repair mitochondrial function.By activating key antioxidant pathways involving nuclear factor ery-throid 2-related factor 2(Nrf2),glutathione peroxidase 4(GPX4),and sirtuin 1(SIRT1),TCM interventions may block lipid peroxida-tion chain reactions,inhibit NPC ferroptosis,and contribute to the prevention and treatment of IVDD.Future research should move beyond the reductionist paradigm of"single target and linear pathway".Future studies should integrate the pathological characteristics of specific TCM patterns,such as Kidney essence deficiency and cold-dampness impediment,and adopt a holistic"disease-pattern-tar-get"approach for model construction and systematic mechanistic investigation.Such systems-level methodologies may provide new insights into the mechanisms by which TCM prevents and treats IVDD and may offer new strategies for innovative drug development.