天然活性成分通过HIF-1α干预椎间盘退变"缺氧-焦亡-炎症"级联反应的研究进展OA

Intervertebral disc degeneration(IVDD)is the core cause of chronic low back pain,which severely impairs patients'quality of life and imposes a heavy social and medical burden.The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α(HIF-1α)is the core pathological mechanism driving the initiation and progression of IVDD.Natural active ingredients derived from traditional Chinese medicine(TCM)have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects,favorable efficacy,and low toxicity.This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients.It is found that natural active ingredients such as baicalein,curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression:targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade,inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals,intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity,and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.