雷公藤治疗动脉粥样硬化的作用机制研究进展
Research Progress on the Mechanisms of Action of Tripterygium wilfordii Hook.f in the Treatment of Atherosclerosis
DOI: 10.12677/acm.2025.152379, PDF,   
作者: 王超英：黑龙江中医药大学第二临床医学院，黑龙江 哈尔滨；陈会君*：黑龙江中医药大学附属第二医院心血管科，黑龙江 哈尔滨
关键词: 雷公藤；机制；动脉粥样硬化；研究进展；Tripterygium wilfordii Hook.f； Mechanism； Atherosclerosis； Research Progress
摘要: 动脉粥样硬化会出现血管内皮损伤，纤维组织增生，脂质沉积、钙质沉着于血管壁，逐渐形成斑块，造成管腔狭窄。动脉粥样硬化主要侵犯大中型动脉血管，是多种心血管疾病病理基础。其病死率呈现下降趋势，但发病率仍在不断增加，所以动脉粥样硬化的预防和治疗仍需重视。雷公藤具有多种活性成分，可通过调节免疫系统、炎症反应、线粒体功能、氧化应激、脂质代谢、血小板功能、血管重塑以及抗血栓形成等多个途径起到抗动脉粥样硬化的作用。雷公藤因其具有多成分、多途径、多靶点、整体性的特点，可更有效抑制动脉粥样硬化对血管的损伤。文章的意义在于系统总结了雷公藤治疗动脉粥样硬化的潜在机制，为雷公藤的临床应用和新药研发提供了理论依据。
Abstract: Atherosclerosis is characterized by endothelial injury, proliferation of fibrous tissue, lipid deposition, and calcium accumulation in the vascular wall, gradually forming plaques that lead to lumen narrowing. Atherosclerosis mainly invades large and medium-sized arterial vessels, and is the pathological basis of many cardiovascular diseases. Its death rate shows a decreasing trend, but the incidence is still increasing, so the prevention and treatment of atherosclerosis still need attention. Tripterygium wilfordii Hook.f has a variety of active components, which can play an anti-atherosclerotic role by regulating the immune system, inflammatory response, mitochondrial function, oxidative stress, lipid metabolism, platelet function, vascular remodeling, and anti-thrombosis in a number of pathways. Because of its multi-component, multi-pathway, multi-target and holistic characteristics, Tripterygium wilfordii Hook.f can more effectively inhibit the damage of atherosclerosis on blood vessels. The significance of the article is that it systematically summarizes the potential mechanism of Tripterygium wilfordiiHook.f in the treatment of atherosclerosis, and provides a theoretical basis for the clinical application of Tripterygium wilfordii Hook.f and the development of new drugs.
文章引用：王超英, 陈会君. 雷公藤治疗动脉粥样硬化的作用机制研究进展[J]. 临床医学进展, 2025, 15(2): 554-562. https://doi.org/10.12677/acm.2025.152379

参考文献

[1] Kobiyama, K. and Ley, K. (2018) Atherosclerosis: A Chronic Inflammatory Disease with an Autoimmune Component. Circulation Research, 123, 1118-1120. [Google Scholar] [CrossRef] [PubMed]
[2] Nedkoff, L., Briffa, T., Zemedikun, D., Herrington, S. and Wright, F.L. (2023) Global Trends in Atherosclerotic Cardiovascular Disease. Clinical Therapeutics, 45, 1087-1091. [Google Scholar] [CrossRef] [PubMed]
[3] 中国医师协会中西医结合分会心血管专业委员会, 中华中医药学会心血管病分会. 动脉粥样硬化中西医防治专家共识(2021年) [J]. 中国中西医结合杂志, 2022, 42(3): 287-293.
[4] 胡德俊, 彭泽燕, 何东初. 雷公藤的药理作用研究进展[J]. 医药导报, 2018, 37(5): 586-592.
[5] Roy, P., Orecchioni, M. and Ley, K. (2021) How the Immune System Shapes Atherosclerosis: Roles of Innate and Adaptive Immunity. Nature Reviews Immunology, 22, 251-265. [Google Scholar] [CrossRef] [PubMed]
[6] Tao, Z., Xiao, Q., Che, X., Zhang, H., Geng, N. and Shao, Q. (2022) Regulating Mitochondrial Homeostasis and Inhibiting Inflammatory Responses through Celastrol. Annals of Translational Medicine, 10, Article 400. [Google Scholar] [CrossRef] [PubMed]
[7] 李世杰, 张诗雨, 孙阳, 等. 雷公藤甲素对ox-LDL诱发的血管内皮细胞炎症反应的抑制作用及机制研究[J]. 世界科学技术-中医药现代化, 2023, 25(4): 1341-1349.
[8] Zhang, G., Qin, Q., Zhang, C., Sun, X., Kazama, K., Yi, B., et al. (2023) NDRG1 Signaling Is Essential for Endothelial Inflammation and Vascular Remodeling. Circulation Research, 132, 306-319. [Google Scholar] [CrossRef] [PubMed]
[9] Engelen, S.E., Robinson, A.J.B., Zurke, Y. and Monaco, C. (2022) Therapeutic Strategies Targeting Inflammation and Immunity in Atherosclerosis: How to Proceed? Nature Reviews Cardiology, 19, 522-542. [Google Scholar] [CrossRef] [PubMed]
[10] Allen, S.D., Liu, Y., Kim, T., Bobbala, S., Yi, S., Zhang, X., et al. (2019) Celastrol-Loaded PEG-b-PPS Nanocarriers as an Anti-Inflammatory Treatment for Atherosclerosis. Biomaterials Science, 7, 657-668. [Google Scholar] [CrossRef] [PubMed]
[11] 程军, 李金平, 田卓, 等. 南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响[J]. 中国病理生理杂志, 2009, 25(3): 601-603.
[12] Tian, S., Wang, Y., Wan, J., Yang, M. and Fu, Z. (2024) Co-Stimulators CD40-CD40L, a Potential Immune-Therapy Target for Atherosclerosis: A Review. Medicine, 103, e37718. [Google Scholar] [CrossRef] [PubMed]
[13] Gu, L., Bai, W., Li, S., Zhang, Y., Han, Y., Gu, Y., et al. (2013) Celastrol Prevents Atherosclerosis via Inhibiting LOX-1 and Oxidative Stress. PLOS ONE, 8, e65477. [Google Scholar] [CrossRef] [PubMed]
[14] Song, C., Wang, Y., Cui, L., Yan, F. and Shen, S. (2019) Triptolide Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Human Endothelial Cells: Involvement of NF-κB Pathway. BMC Complementary and Alternative Medicine, 19, Article No. 198. [Google Scholar] [CrossRef] [PubMed]
[15] 程治平, 余斌, 熊军, 等. 雷公藤内酯醇对ApoE-/-小鼠动脉粥样硬化的作用研究[J]. 海南医学, 2014, 25(12): 1725-1729.
[16] Luo, L. and Yang, T. (2016) Triptolide Inhibits the Progression of Atherosclerosis in Apolipoprotein E−/− Mice. Experimental and Therapeutic Medicine, 12, 2307-2313. [Google Scholar] [CrossRef] [PubMed]
[17] 何为, 潘建青, 曾叶, 等. 雷公藤内酯酮对小鼠腹腔巨噬细胞分泌NO和TNF-α的影响[J]. 华中科技大学学报(医学版), 2005, 34(2): 153-155.
[18] Adebayo, M., Singh, S., Singh, A.P. and Dasgupta, S. (2021) Mitochondrial Fusion and Fission: The Fine‐Tune Balance for Cellular Homeostasis. The FASEB Journal, 35, e21620. [Google Scholar] [CrossRef] [PubMed]
[19] Luan, Y., Ren, K., Luan, Y., Chen, X. and Yang, Y. (2021) Mitochondrial Dynamics: Pathogenesis and Therapeutic Targets of Vascular Diseases. Frontiers in Cardiovascular Medicine, 8, Article 770574. [Google Scholar] [CrossRef] [PubMed]
[20] Hu, M., Luo, Q., Alitongbieke, G., Chong, S., Xu, C., Xie, L., et al. (2017) Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy. Molecular Cell, 66, 141-153.e6. [Google Scholar] [CrossRef] [PubMed]
[21] Vekic, J., Stromsnes, K., Mazzalai, S., Zeljkovic, A., Rizzo, M. and Gambini, J. (2023) Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk. Biomedicines, 11, Article 2897. [Google Scholar] [CrossRef] [PubMed]
[22] Batty, M., Bennett, M.R. and Yu, E. (2022) The Role of Oxidative Stress in Atherosclerosis. Cells, 11, Article 3843. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, S., Xie, S., Gao, Y. and Wang, Y. (2022) Triptolide Alleviates Oxidized LDL-Induced Endothelial Inflammation by Attenuating the Oxidative Stress-Mediated Nuclear Factor-κ B Pathway. Current Therapeutic Research, 97, Article ID: 100683. [Google Scholar] [CrossRef] [PubMed]
[24] Fiorelli, S., Porro, B., Cosentino, N., Di Minno, A., Manega, C.M., Fabbiocchi, F., et al. (2019) Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability: An in Vitro and in Vivo Study. Cells, 8, Article 356. [Google Scholar] [CrossRef] [PubMed]
[25] 李锋, 李义嘉, 李清仙, 等. 雷公藤红素抑制LDL及HAEC细胞氧化损伤作用[J]. 中国药理学通报, 2016, 32(11): 1578-1584.
[26] Yu, X., Tao, W., Jiang, F., Li, C., Lin, J. and Liu, C. (2010) Celastrol Attenuates Hypertension-Induced Inflammation and Oxidative Stress in Vascular Smooth Muscle Cells via Induction of Heme Oxygenase-1. American Journal of Hypertension, 23, 895-903. [Google Scholar] [CrossRef] [PubMed]
[27] Dabravolski, S.A., Sukhorukov, V.N., Kalmykov, V.A., Orekhov, N.A., Grechko, A.V. and Orekhov, A.N. (2022) Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing. International Journal of Molecular Sciences, 23, Article 649. [Google Scholar] [CrossRef] [PubMed]
[28] Zhao, L., Lei, W., Deng, C., Wu, Z., Sun, M., Jin, Z., et al. (2020) The Roles of Liver X Receptor Α in Inflammation and Inflammation‐Associated Diseases. Journal of Cellular Physiology, 236, 4807-4828. [Google Scholar] [CrossRef] [PubMed]
[29] Scorletti, E. and Carr, R.M. (2022) A New Perspective on NAFLD: Focusing on Lipid Droplets. Journal of Hepatology, 76, 934-945. [Google Scholar] [CrossRef] [PubMed]
[30] Shi, Y., Jiang, S., Zhao, T., Gong, Y., Liao, D. and Qin, L. (2020) Celastrol Suppresses Lipid Accumulation through LXRα/ABCA1 Signaling Pathway and Autophagy in Vascular Smooth Muscle Cells. Biochemical and Biophysical Research Communications, 532, 466-474. [Google Scholar] [CrossRef] [PubMed]
[31] 汪瑜翔, 姜爽, 石雅宁, 等. 雷公藤红素通过激活LXRα/ABCA1通路和细胞自噬抑制巨噬细胞脂质蓄积[J]. 生物化学与生物物理进展, 2021, 48(7): 836-845.
[32] Wang, C., Shi, C., Yang, X., Yang, M., Sun, H. and Wang, C. (2014) Celastrol Suppresses Obesity Process via Increasing Antioxidant Capacity and Improving Lipid Metabolism. European Journal of Pharmacology, 744, 52-58. [Google Scholar] [CrossRef] [PubMed]
[33] 信长慧, 张竞超, 张付菊. 雷公藤多苷片对高脂小鼠血脂的影响[J]. 中国现代应用药学, 2018, 35(9): 1351-1354.
[34] Pyrpyris, N., Dimitriadis, K., Beneki, E., Iliakis, P., Soulaidopoulos, S., Tsioufis, P., et al. (2024) LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis. Current Problems in Cardiology, 49, Article ID: 102117. [Google Scholar] [CrossRef] [PubMed]
[35] Mandel, J., Casari, M., Stepanyan, M., Martyanov, A. and Deppermann, C. (2022) Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation. International Journal of Molecular Sciences, 23, Article 3868. [Google Scholar] [CrossRef] [PubMed]
[36] Poznyak, A.V., Orekhova, V.A., Sukhorukov, V.N., Melnichenko, A.A., Pleshko, E.M. and Orekhov, A.N. (2024) Platelet Implication in Atherosclerosis Pathogenesis. Journal of Angiotherapy, 8, 1-8.
[37] Li, X., Zhang, J., Li, Y., Dai, Y., Zhu, H., Jiang, H., et al. (2024) Celastrol Inhibits Platelet Function and Thrombus Formation. Biochemical and Biophysical Research Communications, 693, Article ID: 149366. [Google Scholar] [CrossRef] [PubMed]
[38] Hu, H., Straub, A., Tian, Z., Bassler, N., Cheng, J. and Peter, K. (2009) Celastrol, a Triterpene Extracted from Tripterygium Wilfordii Hook F, Inhibits Platelet Activation. Journal of Cardiovascular Pharmacology, 54, 240-245. [Google Scholar] [CrossRef] [PubMed]
[39] Barreca, M.M., Raimondo, S., Conigliaro, A., Siragusa, S., Napolitano, M., Alessandro, R., et al. (2024) The Combination of Natural Compounds Escin-Bromelain-Ginkgo Biloba-Sage Miltiorrhiza (EBGS) Reduces Platelet Adhesion to TNFα-Activated Vascular Endothelium through FAK Signaling. International Journal of Molecular Sciences, 25, Article 9252. [Google Scholar] [CrossRef] [PubMed]
[40] Ouyang, M., Qin, T., Liu, H., Lu, J., Peng, C. and Guo, Q. (2020) Enhanced Inflammatory Reaction and Thrombosis in High-Fat Diet-Fed Apoe-/- Mice Are Attenuated by Celastrol. Experimental and Clinical Endocrinology & Diabetes, 129, 339-348. [Google Scholar] [CrossRef] [PubMed]
[41] Elmarasi, M., Elmakaty, I., Elsayed, B., Elsayed, A., Zein, J.A., Boudaka, A., et al. (2024) Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis, Hypertension, and Aortic Dissection. Journal of Cellular Physiology, 239, e31200. [Google Scholar] [CrossRef] [PubMed]
[42] Li, J., Liu, C., Shiao, W., Jayakumar, T., Li, Y., Chang, N., et al. (2018) Inhibitory Effect of PDGF-BB and Serum-Stimulated Responses in Vascular Smooth Muscle Cell Proliferation by Hinokitiol via Up-Regulation of P21 and P53. Archives of Medical Science, 14, 579-587. [Google Scholar] [CrossRef] [PubMed]
[43] 谷佳, 贺卫和, 张银羽, 等. 雷公藤红素通过调节血管平滑肌细胞表型转化改善血管重塑的作用机制研究[J]. 中国临床药理学杂志, 2023, 39(14): 2033-2038.
[44] Heun, Y., Gräff, P., Lagara, A., Schelhorn, R., Mettler, R., Pohl, U., et al. (2020) The GEF Cytohesin-2/ARNO Mediates Resistin Induced Phenotypic Switching in Vascular Smooth Muscle Cells. Scientific Reports, 10, Article No. 3672. [Google Scholar] [CrossRef] [PubMed]
[45] Kang, S., Kim, M.S., Kim, H., Kim, Y., Shin, D., Park, J.H.Y., et al. (2012) Celastrol Attenuates Adipokine Resistin‐associated Matrix Interaction and Migration of Vascular Smooth Muscle Cells. Journal of Cellular Biochemistry, 114, 398-408. [Google Scholar] [CrossRef] [PubMed]
[46] Engeland, K. (2022) Cell Cycle Regulation: p53-p21-RB signaling. Cell Death & Differentiation, 29, 946-960. [Google Scholar] [CrossRef] [PubMed]
[47] 罗小平, 徐朝军, 宋岚, 等. 雷公藤甲素诱导人冠状动脉平滑肌细胞凋亡的实验研究[J]. 实用临床医学, 2007, 8(8): 6-9.
[48] Tao, R., Lu, L., Zhang, R., Hu, J., Ni, J. and Shen, W. (2011) Triptolide Inhibits Rat Vascular Smooth Muscle Cell Proliferation and Cell Cycle Progression via Attenuation of ERK1/2 and Rb Phosphorylation. Experimental and Molecular Pathology, 90, 137-142. [Google Scholar] [CrossRef] [PubMed]
[49] Xu, L., Hao, H., Hao, Y., Wei, G., Li, G., Ma, P., et al. (2019) Aberrant MFN2 Transcription Facilitates Homocysteine‐induced VSMCs Proliferation via the Increased Binding of C‐Myc to DNMT1 in Atherosclerosis. Journal of Cellular and Molecular Medicine, 23, 4611-4626. [Google Scholar] [CrossRef] [PubMed]
[50] Shi, Y., Liu, L., Deng, C., Zhao, T., Shi, Z., Yan, J., et al. (2021) Celastrol Ameliorates Vascular Neointimal Hyperplasia through Wnt5a-Involved Autophagy. International Journal of Biological Sciences, 17, 2561-2575. [Google Scholar] [CrossRef] [PubMed]
[51] Bujor, A., Miron, A., Trifan, A., Luca, S.V., Gille, E., Miron, S., et al. (2020) Phytochemicals and Endothelial Dysfunction: Recent Advances and Perspectives. Phytochemistry Reviews, 20, 653-691. [Google Scholar] [CrossRef] 
[52] Li, M., Liu, X., He, Y., Zheng, Q., Wang, M., Wu, Y., et al. (2017) Celastrol Attenuates Angiotensin II Mediated Human Umbilical Vein Endothelial Cells Damage through Activation of Nrf2/ERK1/2/Nox2 Signal Pathway. European Journal of Pharmacology, 797, 124-133. [Google Scholar] [CrossRef] [PubMed]
[53] Huang, Y., Song, C., He, J. and Li, M. (2022) Research Progress in Endothelial Cell Injury and Repair. Frontiers in Pharmacology, 13, Article 997272. [Google Scholar] [CrossRef] [PubMed]
[54] Kim, Y., Pae, H., Park, J.E., Lee, Y.C., Woo, J.M., Kim, N., et al. (2011) Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities. Antioxidants & Redox Signaling, 14, 137-167. [Google Scholar] [CrossRef] [PubMed]
[55] Lu, C., Zhang, X., Zhang, D., Pei, E., Xu, J., Tang, T., et al. (2015) Short Time Tripterine Treatment Enhances Endothelial Progenitor Cell Function via Heat Shock Protein 32. Journal of Cellular Physiology, 230, 1139-1147. [Google Scholar] [CrossRef] [PubMed]
[56] Lu, C., Yu, X., Zuo, K., Zhang, X., Cao, C., Xu, J., et al. (2015) Tripterine Treatment Improves Endothelial Progenitor Cell Function via Integrin-Linked Kinase. Cellular Physiology and Biochemistry, 37, 1089-1103. [Google Scholar] [CrossRef] [PubMed]

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