综述与专论:基于炎症相关信号通路探讨椎间盘退变机制及中医药干预
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1)甘肃中医药大学中医临床学院,兰州 730000;2)甘肃省中医院脊柱骨二科,兰州 730050

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国家自然科学基金(82360947),甘肃省卫健委卫生行业项目(GSWSZD2024-04),国家中医药管理局-重大疑难疾病中西医临床协作项目(ZDYN-2024-A-145)和兰州市科技发展指导性计划项目(2023-ZD-46)资助。


Review: Mechanisms of Intervertebral Disc Degeneration and Traditional Chinese Medicine Intervention Based on Inflammatory-related Signaling Pathways
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1)School of Clinical Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China;2)The Second Department of Spine Surgery, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China

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This work was supported by grants from The National Natural Science Foundation of China (82360947), Health Industry Project of Gansu Provincial Health Commission (GSWSZD2024-04), Clinical Collaboration Project of Integrated Traditional Chinese and Western Medicine for Major and Difficult Diseases, National Administration of Traditional Chinese Medicine (ZDYN-2024-A-145), and Lanzhou Science and Technology Development Guidance Program (2023-ZD-46).

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    摘要:

    椎间盘退变(intervertebral disc degeneration,IVDD)是引发慢性腰背痛的首要致病因素,其病理机制复杂,涉及炎症、基质降解、细胞衰老与死亡等多环节的交互作用。以白介素-1β(interleukin-1β,IL-1β)和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)为核心的促炎轴,通过激活核因子κB(nuclear factor-κB,NF-κB)、丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)、NOD样受体蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体,及磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)等多条关键信号通路,形成促进IVDD进展的核心调控网络。本文系统阐述该网络在介导椎间盘细胞命运和细胞外基质(extracellular matrix,ECM)稳态失衡中的作用,并聚焦中医药“多成分-多靶点-整体调控”的干预特色。研究发现,诸多中药单体(如阿魏酸、芒果苷、丹皮酚等)及复方能够协同调控上述信号枢纽,发挥抗炎、抗氧化、抑制细胞凋亡与焦亡、保护ECM、调节自噬等多重生物学效应,从而有效延缓IVDD进程。然而,现有研究仍多局限于单一成分对单一通路的验证,而对中药复方在多通路动态网络中的系统性调控机制,以及相关临床转化(如精准递送系统)仍缺乏深入探索。未来研究需整合组学与人工智能、类器官/器官芯片模型等技术,以全面揭示中医药防治IVDD的科学内涵,并推动其向临床精准干预策略的实质性转化。

    Abstract:

    Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

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杨龙,王晨晨,黄涛,刘鑫峰,何林林,张天龙,张彦军.综述与专论:基于炎症相关信号通路探讨椎间盘退变机制及中医药干预[J].生物化学与生物物理进展,2026,53(5):1115-1131 YANG Long, WANG Chen-Chen, HUANG Tao, LIU Xin-Feng, HE Lin-Lin, ZHANG Tian-Long, ZHANG Yan-Jun.Review: Mechanisms of Intervertebral Disc Degeneration and Traditional Chinese Medicine Intervention Based on Inflammatory-related Signaling Pathways[J]. Progress in Biochemistry and Biophysics,2026,53(5):1115-1131

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  • 收稿日期:2026-01-20
  • 最后修改日期:2026-05-18
  • 录用日期:2026-04-14
  • 在线发布日期: 2026-04-15
  • 出版日期: 2026-05-28
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