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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
                                       Δ


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          王 浩 ,陈仁场 ,黄文浩 ,周冰倩 ,郑喜秋 ,王佳浩 ,李念虎 ,吴亚东 (1.山东中医药大学第一临床医学院,
                                                   1
                 1*
          济南 250014;2.山东中医药大学附属医院脊柱脊髓科,济南 250014;3.日照市中医医院脊柱骨科,山东 日照
          276800)
          中图分类号  R274      文献标志码  A      文章编号  1001-0408(2026)08-1092-07
          DOI  10.6039/j.issn.1001-0408.2026.08.21
          摘   要  椎间盘退变(IVDD)是慢性下腰痛的核心病因,可严重降低患者的生活质量,并造成沉重的社会医疗负担。缺氧诱导因
          子1α(HIF-1α)介导的“缺氧-焦亡-炎症”级联反应是驱动IVDD发生发展的核心病理机制。中药来源的天然活性成分因多靶点作
          用、疗效显著、低毒性等优势,已成为IVDD防治领域的研究热点。本文系统综述了HIF-1α介导退变髓核组织“缺氧-焦亡-炎症”
          级联反应的机制及相关天然活性成分的干预作用,发现黄芩素、姜黄素、白藜芦醇等天然活性成分,可分别从靶向HIF-1α氧感知
          通路以阻断焦亡病理级联启动、抑制核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3炎症小体活化以切断炎症
          信号级联放大、干预消皮素D介导的焦亡执行阶段以保护细胞膜完整性、促进细胞外基质修复与基质稳态重建四个核心环节,多
          靶点干预HIF-1α介导的病理级联反应,从而延缓IVDD进展。
          关键词  缺氧诱导因子1α;天然活性成分;髓核组织;缺氧;焦亡;炎症

          Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade
          in intervertebral disc degeneration through HIF-1α
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          WANG Hao ,CHEN Renchang ,HUANG Wenhao ,ZHOU Bingqian ,ZHENG Xiqiu ,WANG Jiahao , LI Nianhu ,
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          WU Yadong (1.  First  Clinical  Medical  College,  Shandong  University  of  Traditional  Chinese  Medicine,  Jinan
                     1, 3
          250014, China;2. Dept. of Spine and Spinal Cord, the Affiliated Hospital of Shandong University of Traditional
          Chinese  Medicine,  Jinan  250014,  China;3.  Dept.  of  Spine  Orthopedics,  Rizhao  Traditional  Chinese  Medicine
          Hospital, Shandong Rizhao 276800, China)
          ABSTRACT    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.
          KEYWORDS     HIF-1α; natural active ingredients; nucleus pulposus tissue; hypoxia; pyroptosis; inflammation

              Δ 基金项目 山东省自然科学基金项目(No.ZR2021LZY006,No.
                                                                  椎间盘退变(intervertebral disc degeneration,IVDD)
          ZR2023MH063)
             *第一作者 硕士研究生。研究方向:脊柱脊髓与骨关节疾病。                     是慢性下腰痛的核心病因,临床以局部疼痛为主要表
          E-mail:1363091613@qq.com
                                                              现,常伴随坐骨神经痛和运动功能障碍,可严重降低患
              # 通信作者 副主任医师,硕士生导师。研究方向:脊柱脊髓与骨
          关节疾病。E-mail:2022140062@sdutcm.edu.cn                者的生活质量,并带来沉重的社会医疗负担                   [1―2] 。IVDD


          · 1092 ·    China Pharmacy  2026 Vol. 37  No. 8                              中国药房  2026年第37卷第8期
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