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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
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1, 3 #
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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,
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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
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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

