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| 程序性细胞死亡：中药防治心肌纤维化的关键靶点与多维调控策略 |
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何思思1, 王钰瑶1, 张莹莹1, 李桦1, 王泰一2,3,4
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1.山东中医药大学, 中医药创新研究院, 济南 250355;2.山东中医药大学, 针灸研究院, 济南 250355;3.山东中医药大学, 中医药经典理论教育部重点实验室, 济南 250355;4.山东中医药大学, 山东省中医药基础理论创新与应用研究重点实验室, 济南 250355
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| 摘要: |
| 心肌纤维化（MF） 是多种心血管疾病的共同病理基础，主要表现为心肌间质中如Ⅰ型及Ⅲ型胶原等细胞外基质（ECM） 蛋白异常过度沉积，导致的心肌硬化、顺应性下降，并导致心室重构及心力衰竭的发生。程序性细胞死亡（PCD）（如凋亡、焦亡、坏死性凋亡、铁死亡等）异常激活是心肌损伤、炎症放大及纤维化进展的核心始动环节，各通路交叉互作形成死亡调控网络，是慢性纤维化难以逆转的关键原因。中药单体凭借多靶点、跨通路协同调控特性，可精准干预PCD网络关键节点，抑制心肌细胞异常死亡、减轻炎症反应、阻断成纤维细胞活化与胶原过度沉积，在抗心肌纤维化中展现独特优势。文章系统梳理PCD各亚型在心肌纤维化中的调控机制，总结中药单体靶向PCD网络的干预效应与分子通路，明确中药多通路适度干预的作用模式，并提出网络药理学与PCD调控网络靶向是未来中药抗心肌纤维化研究的核心方向，为中医药现代化与抗纤维化新药研发提供理论依据与新思路。 |
| 关键词: 心肌纤维化 程序性细胞死亡 中药单体 细胞外基质 心室重构 |
| DOI：10.11656/j.issn.1673-9043.2026.09.14 |
| 分类号:R542.23 |
| 基金项目:国家自然科学基金面上项目（53202319）；泰山学者青年专家项目（tsqn202306188）。 |
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| Programmed cell death: key targets and multidimensional modulation strategies of traditional Chinese medicine for prevention and treatment of myocardial fibrosis |
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HE Sisi1, WANG Yuyao1, ZHANG Yingying1, LI Hua1, WANG Taiyi2,3,4
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1.Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;2.Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;3.Key Laboratory of Traditional Chinese Medicine Classic Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;4.Shandong Provincial Key Laboratory of Innovation and Applied Research of Basic Theories of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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| Abstract: |
| Myocardial fibrosis（MF） is a common pathological basis for various cardiovascular diseases，characterized by excessive deposition of extracellular matrix（ECM） proteins，such as type I and type III collagen，in the myocardial interstitium. This results in myocardial stiffness，decreased compliance，ventricular remodeling，and heart failure. Aberrant activation of programmed cell death（PCD），including apoptosis，pyroptosis，necroptosis，and ferroptosis，serves as a core initiator of myocardial injury，inflammatory amplification，and fibrotic progression. The crosstalk among these pathways forms a death regulatory network，which is a key reason for the irreversibility of chronic fibrosis. Traditional Chinese medicine（TCM） monomers exhibit unique advantages against MF due to their multi-target and cross-pathway regulatory properties. They can precisely intervene in key nodes of the PCD network，inhibit abnormal cardiomyocyte death，alleviate inflammation，block fibroblast activation，and reduce excessive collagen deposition. This paper systematically reviews the regulatory mechanisms of PCD subtypes in myocardial fibrosis，summarizes the intervention effects and molecular pathways of TCM monomers targeting the PCD network，and clarifies the multi-pathway modulatory intervention strategies of TCM. Furthermore，we propose that network pharmacology and targeting the PCD regulatory network will be the core directions for future research on anti-fibrotic therapy of TCM，providing a theoretical basis and new insights for the modernization of traditional Chinese medicine and the development of new anti-fibrotic drugs. |
| Key words: myocardial fibrosis programmed cell death traditional Chinese medicine monomer extracellular matrix ventricular remodeling |
