
浏览全部资源
扫码关注微信
1.山东中医药大学第一临床医学院,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
硕士研究生。研究方向:脊柱脊髓与骨关节疾病。 E-mail:1363091613@qq.com
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
收稿:2025-11-03,
修回:2026-03-16,
录用:2026-03-16,
纸质出版:2026-04-30
移动端阅览
王浩,陈仁场,黄文浩,等.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 [J].中国药房,2026,37(08):1092-1098.
WANG Hao,CHEN Renchang,HUANG Wenhao,et al.Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade in intervertebral disc degeneration through HIF-1α[J].ZHONGGUO YAOFANG,2026,37(08):1092-1098.
王浩,陈仁场,黄文浩,等.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 [J].中国药房,2026,37(08):1092-1098. DOI: 10.6039/j.issn.1001-0408.2026.08.21.
WANG Hao,CHEN Renchang,HUANG Wenhao,et al.Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade in intervertebral disc degeneration through HIF-1α[J].ZHONGGUO YAOFANG,2026,37(08):1092-1098. DOI: 10.6039/j.issn.1001-0408.2026.08.21.
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。
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.
KNEZEVIC N N , CANDIDO K D , VLAEYEN J W S , et al . Low back pain [J ] . Lancet , 2021 , 398 ( 10294 ): 78 - 92 .
GBD 2021 Low Back Pain Collaborators . Global,regional,and national burden of low back pain,1990-2020,its attributable risk factors,and projections to 2050:a sys-tematic analysis of the Global Burden of Disease Study 2021 [J ] . Lancet Rheumatol , 2023 , 5 ( 6 ): e316 - e329 .
GRANT M P , ALAD M , YOUSEF F , et al . Link N directly targets IL-1β to suppress inflammation and regulate sensory pain in intervertebral disc degeneration [J ] . Biomolecules , 2025 , 15 ( 4 ): 603 .
XU X Y , PANG Y , FAN X Q . Mitochondria in oxidative stress,inflammation and aging:from mechanisms to therapeutic advances [J ] . Signal Transduct Target Ther , 2025 , 10 ( 1 ): 190 .
FAN C Y , WANG W , YU Z L , et al . M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis [J ] . J Nanobiotechnol , 2024 , 22 ( 1 ): 301 .
SIEBUHR A S , WERKMANN D , BAY-JENSEN A C , et al . The anti-ADAMTS-5 nanobody ® M6495 protects cartilage degradation ex vivo [J ] . Int J Mol Sci , 2020 , 21 ( 17 ): 5992 .
TANG J N , LUO Y X , WANG Q R , et al . Stimuli-responsive delivery systems for intervertebral disc degen-eration [J ] . Int J Nanomed , 2024 , 19 : 4735 - 4757 .
LIU Z C , ZHENG J C , DING T , et al . HIF-1α protects nucleus pulposus cells from oxidative stress-induced mitochondrial impairment through PDK-1 [J ] . Free Radic Biol Med , 2024 , 224 : 39 - 49 .
YANG H , LIU M Z , SONG S Q , et al . HIF-1α promotes inflammatory responses in Aspergillus fumigatus keratitis by activating pyroptosis through caspase-8/GSDMD pathway [J ] . Invest Ophthalmol Vis Sci , 2025 , 66 ( 6 ): 32 .
YUAN D , GUAN S X , WANG Z , et al . HIF-1α aggravated traumatic brain injury by NLRP3 inflammasome-mediated pyroptosis and activation of microglia [J ] . J Chem Neuroanat , 2021 , 116 : 101994 .
ZHAO K C , AN R , XIANG Q , et al . Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration [J ] . Cell Prolif , 2021 , 54 ( 1 ): e12941 .
WANG G F , WANG J S , LI X , et al . Hypoxia and TNF-α synergistically induce expression of IL-6 and IL-8 in human fibroblast-like synoviocytes via enhancing TAK1/NF-κB/HIF-1α signaling [J ] . Inflammation , 2023 , 46 ( 3 ): 912 - 924 .
DEVANT P , KAGAN J C . Molecular mechanisms of gasdermin D pore-forming activity [J ] . Nat Immunol , 2023 , 24 ( 7 ): 1064 - 1075 .
RAGHURAM G V , TRIPATHY B K , AVADHANI K , et al . Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells [J ] . Cell Death Discov , 2024 , 10 ( 1 ): 30 .
LUO J Y , YANG Y X , WANG X , et al . Role of pyroptosis in intervertebral disc degeneration and its therapeutic implications [J ] . Biomolecules , 2022 , 12 ( 12 ): 1804 .
HE R J , WANG Z , CUI M , et al . HIF1A Alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy [J ] . Autophagy , 2021 , 17 ( 11 ): 3338 - 3360 .
杜红丽 , 张晨宇 , 赵清 . 黄芩素通过调节HIF-1α/VEGF信号通路抑制类风湿关节炎大鼠的炎症反应和病理性血管生成 [J ] . 中国病理生理杂志 , 2022 , 38 ( 12 ): 2213 - 2219 .
CHEN Y , ZHANG J Y , ZHANG M Q , et al . Baicalein resensitizes tamoxifen-resistant breast cancer cells by reducing aerobic glycolysis and reversing mitochondrial dysfunction via inhibition of hypoxia-inducible factor-1α [J ] . Clin Transl Med , 2021 , 11 ( 11 ): e577 .
HAN T H , PARK M K , NAKAMURA H , et al . Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells [J ] . Biomed Pharmacother , 2022 , 146 : 112500 .
DING T , YI T T , LI Y , et al . Luteolin attenuates lupus nephritis by regulating macrophage oxidative stress via HIF-1α pathway [J ] . Eur J Pharmacol , 2023 , 953 : 175823 .
WANG X , YU H J , ZHANG Y H , et al . Curcumin alle-viates osteoarthritis through the p38MAPK pathway:network pharmacological prediction and experimental confirmation [J ] . J Inflamm Res , 2024 , 17 : 5039 - 5056 .
WAHYUNINGSIH S P A , DEWI F R P , HSAN A S Y , et al . The regulation of hypoxia inducible factor(HIF)1α expression by quercetin:an in silico study [J ] . Acta Inform Med , 2022 , 30 ( 2 ): 96 - 99 .
JIANG T T , JI C L , YU L J , et al . Resveratrol-induced SIRT1 activation inhibits glycolysis-fueled angiogenesis under rheumatoid arthritis conditions independent of HIF-1α [J ] . Inflamm Res , 2023 , 72 ( 5 ): 1021 - 1035 .
GUO L , ZHANG X L , LV N , et al . Therapeutic role and potential mechanism of resveratrol in atherosclerosis:TLR4/NF-κB/HIF-1α [J ] . Mediators Inflamm , 2023 , 2023 : 1097706 .
KIM S R , SEONG K J , KIM W J , et al . Epigallocatechin gallate protects against hypoxia-induced inflammation in microglia via NF-κB suppression and Nrf-2/HO-1 activation [J ] . Int J Mol Sci , 2022 , 23 ( 7 ): 4004 .
DING M Y , NING C Q , CHEN S R , et al . Discovery of natural product derivative triptolidiol as a direct NLRP3 inhibitor by reducing K63-specific ubiquitination [J ] . Bri-tish J Pharmacology , 2025 , 182 ( 20 ): 4876 - 4893 .
TANG K , SU W H , HUANG C H , et al . Notoginsenoside R 1 suppresses inflammatory response and the pyroptosis of nucleus pulposus cells via inactivating NF-κB/NLRP3 pathways [J ] . Int Immunopharmacol , 2021 ,101(Pt.B): 107866 .
DAI W Y , LUO Z P . Paeoniflorin inhibits pyroptosis of nucleus pulposus cells in an acidic environment and alle-viates the degeneration of the intervertebral disc in rats [J ] . Cell Signal , 2022 , 91 : 110243 .
LIU Z Y , YAO X Q , SUN B H , et al . Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury [J ] . Free Radic Biol Med , 2021 , 168 : 142 - 154 .
PARK J Y , LEE S J . Myricetin alleviates the mechanism of IL-1β production caused by the endocrine-disrupting chemical Di(2-ethylhexyl)phthalate in RAW 264.7 cells [J ] . Tissue Cell , 2025 , 93 : 102683 .
刘泽萱 , 韩易言 , 关雪峰 , 等 . 基于NF-κB/NLRP3/caspase-1信号轴探讨牛膝皂苷Ⅰ抑制软骨细胞焦亡的研究 [J ] . 中国临床药理学杂志 , 2025 , 41 ( 2 ): 198 - 202 .
WANG L , XIE X H , CHEN Q Y , et al . Puerarin reduces diabetic nephropathy-induced podocyte pyroptosis by modulating the SIRT1/NLRP3/caspase-1 pathway [J ] . Mol Cell Endocrinol , 2025 , 595 : 112409 .
MENG Z Q , GAO M , WANG C Y , et al . Apigenin alle-viated high-fat-diet-induced hepatic pyroptosis by mitophagy-ROS-CTSB-NLRP3 pathway in mice and AML12 cells [J ] . J Agric Food Chem , 2023 , 71 ( 18 ): 7032 - 7045 .
LI Y , OU S T , LIU Q , et al . Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-κB pathway [J ] . Acta Cir Bras , 2022 , 37 ( 6 ): e370601 .
CHEN J , ZHANG B , WU L W , et al . Ginsenoside Rg 3 exhibits anti-catabolic and anti-apoptotic effects in IL-1β treated human disc nucleus pulposus cells and in a rat model of disc degeneration by inactivating the MAPK pathway [J ] . Cell Mol Biol , 2024 , 70 ( 1 ): 233 - 238 .
FENG S , CONG H , JI L . Salvianolic acid a exhibits anti-inflammatory and antiarthritic effects via inhibiting NF-κB and p38/MAPK pathways [J ] . Drug Des Devel Ther , 2020 , 14 : 1771 - 1778 .
WANG K , CHEN T T , YING X Z , et al . Ligustilide alle-viated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo [J ] . Int Immunopharmacol , 2019 , 69 : 398 - 407 .
WANG D , CAI X H , XU F , et al . Ganoderic acid A alle-viates the degeneration of intervertebral disc via suppressing the activation of TLR4/NLRP3 signaling pathway [J ] . Bioengineered , 2022 , 13 ( 5 ): 11684 - 11693 .
WU H J , ZHANG M H , LI W H , et al . Stachydrine attenu-ates IL-1β-induced inflammatory response in osteoarthritis chondrocytes through the NF-κB signaling pathway [J ] . Chem Biol Interact , 2020 , 326 : 109136 .
黄涛 , 范明宇 , 周少怀 , 等 . Wnt/β-catenin通路下穿心莲内酯对TBHP诱导髓核细胞稳态的作用 [J ] . 中国老年学杂志 , 2024 , 44 ( 22 ): 5574 - 5578 .
CHEN T Q , LI P F , QIU J C , et al . Aloin regulates matrix metabolism and apoptosis in human nucleus pulposus cells via the TAK1/NF-κB/NLRP3 signaling pathway [J ] . Stem Cells Int , 2022 , 2022 : 5865011 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621