从线粒体质量控制角度探讨黄芪–丹参治疗心肌缺血再灌注损伤的研究进展
Advances in the Treatment of Myocardial Ischemia-Reperfusion Injury with Astragalus membranaceus and Salvia miltiorrhiza: A Mitochondrial Quality Control Perspective
DOI: 10.12677/tcm.2026.1510610, PDF,   
作者: 段日鑫*：黑龙江中医药大学研究生院，黑龙江 哈尔滨；崔健昆#：黑龙江中医药大学研究生院，黑龙江 哈尔滨；黑龙江中医药大学附属第一医院心血管病四科，黑龙江 哈尔滨
关键词: 心肌缺血再灌注损伤；线粒体质量控制；黄芪；丹参；Myocardial Ischemia-Reperfusion Injury； Mitochondrial Quality Control； Astragalus membranaceus； Salvia miltiorrhiza
摘要: 心肌缺血再灌注损伤(MIRI)是一种在心肌供血中断后恢复血流供应时，心肌损伤反而进一步加重的病理过程。黄芪–丹参作为临床常用的益气活血经典药对，二者配伍可通过多靶点调控线粒体质量控制(MQC)网络有效改善MIRI。本文从恢复线粒体生物合成、重塑线粒体动力学平衡、双向调控线粒体自噬、抗氧化应激与抑制mPTP开放等方面，系统梳理黄芪–丹参活性成分防治MIRI的作用机制研究，为其临床应用和MIRI的治疗提供参考。
Abstract: Myocardial ischemia-reperfusion injury (MIRI) refers to a pathological condition where myocardial damage is aggravated paradoxically after blood flow is restored following myocardial ischemia. Astragalus membranaceus and Salvia miltiorrhiza, a classic herb pair for replenishing qi and activating blood circulation in clinical practice, can effectively alleviate MIRI via multi-target regulation of the mitochondrial quality control (MQC) network. This paper systematically reviews the molecular mechanisms of active ingredients derived from this herb pair against MIRI, covering restoration of mitochondrial biogenesis, remodeling of mitochondrial dynamic balance, bidirectional modulation of mitophagy, anti-oxidative stress effects and suppression of mPTP opening. It provides theoretical references for its clinical application and therapeutic research of MIRI.
文章引用：段日鑫, 崔健昆. 从线粒体质量控制角度探讨黄芪–丹参治疗心肌缺血再灌注损伤的研究进展[J]. 中医学, 2026, 15(10): 727-737. https://doi.org/10.12677/tcm.2026.1510610

参考文献

[1] Sun, J., Qiao, Y., Zhao, M., Magnussen, C.G. and Xi, B. (2023) Global, Regional, and National Burden of Cardiovascular Diseases in Youths and Young Adults Aged 15-39 years in 204 Countries/Territories, 1990-2019: A Systematic Analysis of Global Burden of Disease Study 2019. BMC Medicine, 21, Article No. 222.
https://doi.org/10.1186/s12916-023-02925-4
[2] Zhang, S., Yan, F., Luan, F., Chai, Y., Li, N., Wang, Y., et al. (2024) The Pathological Mechanisms and Potential Therapeutic Drugs for Myocardial Ischemia Reperfusion Injury. Phytomedicine, 129, Article ID: 155649.
https://doi.org/10.1016/j.phymed.2024.155649
[3] Zhao, Y., Liang, J., Liu, X., Li, H., Chang, C., Gao, P., et al. (2024) Tcap Deficiency Impedes Striated Muscle Function and Heart Regeneration with Elevated ROS and Autophagy. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1870, Article ID: 167485.
https://doi.org/10.1016/j.bbadis.2024.167485
[4] Dikalov, S., Panov, A. and Dikalova, A. (2024) Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions. International Journal of Molecular Sciences, 25, Article No. 6498.
https://doi.org/10.3390/ijms25126498
[5] Boveris, A. and Chance, B. (1973) The Mitochondrial Generation of Hydrogen Peroxide. General Properties and Effect of Hyperbaric Oxygen. Biochemical Journal, 134, 707-716.
https://doi.org/10.1042/bj1340707
[6] Hong, Y., Boiti, A., Vallone, D. and Foulkes, N.S. (2024) Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution. Antioxidants, 13, Article No. 312.
https://doi.org/10.3390/antiox13030312
[7] Ay, Y.A., Yurdgulu, E.E., Bayir, Y. and Halici, Z. (2025) The Role and Behavior of Voltage-Gated Calcium Channels in Ischemia/Reperfusion. Cellular Signalling, 136, Article ID: 112107.
https://doi.org/10.1016/j.cellsig.2025.112107
[8] Robichaux, D.J., Harata, M., Murphy, E. and Karch, J. (2023) Mitochondrial Permeability Transition Pore-Dependent Necrosis. Journal of Molecular and Cellular Cardiology, 174, 47-55.
https://doi.org/10.1016/j.yjmcc.2022.11.003
[9] Algoet, M., Janssens, S., Himmelreich, U., Gsell, W., Pusovnik, M., Van den Eynde, J., et al. (2023) Myocardial Ischemia-Reperfusion Injury and the Influence of Inflammation. Trends in Cardiovascular Medicine, 33, 357-366.
https://doi.org/10.1016/j.tcm.2022.02.005
[10] Du, C., Yu, Y., Li, M., Zhou, J., Wang, Y., Guo, X., et al. (2026) Bridging Tradition and Modernity: Mitochondrial Dynamics as a Traditional Chinese Medicine Therapeutic Target in Cardiovascular Disease. Chinese Medicine, 21, Article No. 65.
https://doi.org/10.1186/s13020-025-01225-8
[11] 张佳丽, 张宇彬, 宋若莹, 等. 基于线粒体自噬从“虚气留滞”理论探讨原发性骨质疏松症的病机与治疗[J]. 中国实验方剂学杂志, 2026, 32(20): 230-241.
[12] 李静, 钟森杰, 匡慧芳, 等. 基于“虚气留滞”理论探析心肌能量底物代谢重构的病机与中药干预研究进展[J]. 中国实验方剂学杂志, 2023, 29(17): 195-202.
[13] Sygitowicz, G. and Sitkiewicz, D. (2022) Mitochondrial Quality Control: The Role in Cardiac Injury. Frontiers in Bioscience-Landmark, 27, Article No. 96.
https://doi.org/10.31083/j.fbl2703096
[14] Kuznetsov, A.V., Margreiter, R., Ausserlechner, M.J. and Hagenbuchner, J. (2022) The Complex Interplay between Mitochondria, ROS and Entire Cellular Metabolism. Antioxidants (Basel), 11, Article No. 1995.
https://doi.org/10.3390/antiox11101995
[15] 魏旋, 刘吉勇, 张文丽, 等. 靶向线粒体质量控制防治脑缺血再灌注损伤的研究进展[J]. 中国中药杂志, 2022, 47(16): 4305-4313.
[16] Hernandez‐Resendiz, S., Prunier, F., Girao, H., Dorn, G. and Hausenloy, D.J. (2020) Targeting Mitochondrial Fusion and Fission Proteins for Cardioprotection. Journal of Cellular and Molecular Medicine, 24, 6571-6585.
https://doi.org/10.1111/jcmm.15384
[17] Grimm, S. and Brdiczka, D. (2007) The Permeability Transition Pore in Cell Death. Apoptosis, 12, 841-855.
https://doi.org/10.1007/s10495-007-0747-3
[18] Ikeda, Y., Shirakabe, A., Brady, C., Zablocki, D., Ohishi, M. and Sadoshima, J. (2015) Molecular Mechanisms Mediating Mitochondrial Dynamics and Mitophagy and Their Functional Roles in the Cardiovascular System. Journal of Molecular and Cellular Cardiology, 78, 116-122.
https://doi.org/10.1016/j.yjmcc.2014.09.019
[19] Tong, M., Zablocki, D. and Sadoshima, J. (2020) The Role of Drp1 in Mitophagy and Cell Death in the Heart. Journal of Molecular and Cellular Cardiology, 142, 138-145.
https://doi.org/10.1016/j.yjmcc.2020.04.015
[20] Sharp, W.W., Fang, Y.H., Han, M., Zhang, H.J., Hong, Z., Banathy, A., et al. (2014) Dynamin‐Related Protein 1 (Drp1)‐Mediated Diastolic Dysfunction in Myocardial Ischemia‐Reperfusion Injury: Therapeutic Benefits of Drp1 Inhibition to Reduce Mitochondrial Fission. The FASEB Journal, 28, 316-326.
https://doi.org/10.1096/fj.12-226225
[21] Piao, L., Fang, Y., Fisher, M., Hamanaka, R.B., Ousta, A., Wu, R., et al. (2024) Dynamin‐Related Protein 1 Is a Critical Regulator of Mitochondrial Calcium Homeostasis during Myocardial Ischemia/Reperfusion Injury. The FASEB Journal, 38, e23379.
https://doi.org/10.1096/fj.202301040rr
[22] Fogo, G.M., Raghunayakula, S., Emaus, K.J., Torres Torres, F.J., Wider, J.M. and Sanderson, T.H. (2024) Mitochondrial Membrane Potential and Oxidative Stress Interact to Regulate Oma1‐Dependent Processing of Opa1 and Mitochondrial Dynamics. The FASEB Journal, 38, e70066.
https://doi.org/10.1096/fj.202400313r
[23] Wu, J., Chen, H., Qin, J., Chen, N., Lu, S., Jin, J., et al. (2021) Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1‐Mediated Mitochondrial Fission after Cardiac Arrest‐Induced Myocardial Damage. Oxidative Medicine and Cellular Longevity, 2021, Article ID: 8865762.
https://doi.org/10.1155/2021/8865762
[24] Yu, J., He, J., Yang, W., Wang, X., Shi, G., Duan, Y., et al. (2021) Diabetes Impairs the Protective Effects of Sevoflurane Postconditioning in the Myocardium Subjected to Ischemia/Reperfusion Injury in Rats: Important Role of Drp1. BMC Cardiovascular Disorders, 21, Article No. 96.
https://doi.org/10.1186/s12872-021-01906-w
[25] Zhao, X., Wang, Z., Wang, L., Jiang, T., Dong, D. and Sun, M. (2024) The PINK1/Parkin Signaling Pathway-Mediated Mitophagy: A Forgotten Protagonist in Myocardial Ischemia/Reperfusion Injury. Pharmacological Research, 209, Article ID: 107466.
https://doi.org/10.1016/j.phrs.2024.107466
[26] Newton, K., Strasser, A., Kayagaki, N. and Dixit, V.M. (2024) Cell Death. Cell, 187, 235-256.
https://doi.org/10.1016/j.cell.2023.11.044
[27] Tang, L., Zhang, W., Liao, Y., Wang, W., Deng, X., Wang, C., et al. (2025) Autophagy: A Double-Edged Sword in Ischemia-Reperfusion Injury. Cellular & Molecular Biology Letters, 30, Article No. 42.
https://doi.org/10.1186/s11658-025-00713-x
[28] Fei, Q., Liu, J., Qiao, L., Zhang, M., Xia, H., Lu, D., et al. (2023) Mst1 Attenuates Myocardial Ischemia/Reperfusion Injury Following Heterotopic Heart Transplantation in Mice through Regulating Keap1/Nrf2 Axis. Biochemical and Biophysical Research Communications, 644, 140-148.
https://doi.org/10.1016/j.bbrc.2022.12.087
[29] Li, Y., Ding, N., Liu, X., Si, Q., Wang, Y., Li, C., et al. (2026) The Disrupted Mitochondrial Quality Control Network: A Unifying Mechanism and Therapeutic Target for Chemotherapy-Induced Multi-Organ Toxicity. Biology, 15, Article No. 230.
https://doi.org/10.3390/biology15030230
[30] Cox, A.G., Winterbourn, C.C. and Hampton, M.B. (2009) Mitochondrial Peroxiredoxin Involvement in Antioxidant Defence and Redox Signalling. Biochemical Journal, 425, 313-325.
https://doi.org/10.1042/bj20091541
[31] Juricic, S., Klac, J., Stojkovic, S., Beleslin, B., Tesic, M., Jovanovic, I., et al. (2026) Molecular and Cellular Mechanisms of Myocardial Ischemia and Reperfusion Injury: A Narrative Review. Cells, 15, Article No. 265.
https://doi.org/10.3390/cells15030265
[32] Bernardi, P. and Di Lisa, F. (2015) The Mitochondrial Permeability Transition Pore: Molecular Nature and Role as a Target in Cardioprotection. Journal of Molecular and Cellular Cardiology, 78, 100-106.
https://doi.org/10.1016/j.yjmcc.2014.09.023
[33] 郭帅杰, 李思耐, 刘卫红, 等. 中医气虚血瘀证斑马鱼模型的构建与评价[J]. 世界中医药, 2023, 18(6): 778-782.
[34] 李娜, 姚魁武. 从“气虚血瘀”病机探析线粒体动力学治疗缺血性心脏病的病理机制[J]. 中华中医药学刊, 2023, 41(2): 119-123.
[35] 曾清华, 黄爱思, 施敏, 等. 益心泰对慢性心力衰竭气虚血瘀证大鼠线粒体生物发生的影响[J]. 中国中医药信息杂志, 2026, 33(7): 100-107.
[36] 马莉, 赵俊杰, 王鹏, 等. 黄芪甲苷通过PINK1/parkin通路介导的线粒体自噬途径减轻大鼠脑缺血再灌注损伤[J]. 中国病理生理志, 2025, 41(3): 501-508.
[37] Yang, C., Pan, Q., Ji, K., Tian, Z., Zhou, H., Li, S., et al. (2023) Review on the Protective Mechanism of Astragaloside IV against Cardiovascular Diseases. Frontiers in Pharmacology, 14, Article ID: 1187910.
https://doi.org/10.3389/fphar.2023.1187910
[38] Yuan, H.J., Han, Q.C., Yu, Y.D., Yu, H., Liu, X., Xue, Y., et al. (2025) Calycosin Attenuates Mitochondrial Damage and Pyroptosis in Heart Failure via the Nrf2/ROS/TXNIP Pathway. International Journal of Molecular Medicine, 56, Article No. 212.
https://doi.org/10.3892/ijmm.2025.5653
[39] 张彐宁, 靳晓飞, 张怡, 等. 黄芪中毛蕊异黄酮不同剂量对脑缺血再灌注大鼠神经细胞的保护作用[J]. 河北中医药学报, 2022, 37(3): 43-47.
[40] 范宗静, 谢连娣, 崔杰, 等. 黄芪多糖后处理通过抑制线粒体损伤介导的凋亡保护心肌缺血再灌注损伤[J]. 辽宁中医志, 2018, 45(7): 1357-1360.
[41] Wang, D.S., Yan, L.Y., Yang, D.Z., Lyu, Y., Fang, L., Wang, S., et al. (2020) Formononetin Ameliorates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing the ROS-TXNIP-NLRP3 Pathway. Biochemical and Biophysical Research Communications, 525, 759-766.
https://doi.org/10.1016/j.bbrc.2020.02.147
[42] Zhai, P., Chen, Q., Wang, X., Ouyang, X., Yang, M., Dong, Y., et al. (2024) The Combination of Tanshinone IIA and Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting the STING Pathway. Chinese Medicine, 19, Article No. 34.
https://doi.org/10.1186/s13020-024-00908-y
[43] Hu, T., Zou, H.X., Le, S.Y., Wang, Y.R., Qiao, Y.M., Yuan, Y., et al. (2023) Tanshinone IIA Confers Protection against Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis and Apoptosis via VDAC1. International Journal of Molecular Medicine, 52, Article No. 109.
https://doi.org/10.3892/ijmm.2023.5312
[44] Wei, X.H., Chen, J., Wu, X.F., Zhang, Q., Xia, G., Chu, X., et al. (2025) Salvianolic Acid B Alleviated Myocardial Ischemia-Reperfusion Injury via Modulating SIRT3-Mediated Crosstalk between Mitochondrial ROS and NLRP3. Phytomedicine, 136, Article ID: 156260.
https://doi.org/10.1016/j.phymed.2024.156260
[45] Lu, B., Li, J., Gui, M., Yao, L., Fan, M., Zhou, X., et al. (2022) Salvianolic Acid B Inhibits Myocardial I/R-Induced ROS Generation and Cell Apoptosis by Regulating the TRIM8/GPX1 Pathway. Pharmaceutical Biology, 60, 1458-1468.
https://doi.org/10.1080/13880209.2022.2096644
[46] 李思蒙, 陈建宁, 申思满, 等. 丹酚酸B通过抑制Sirt1蛋白降解促进心肌细胞线粒体功能稳态和改善缺血再灌注小鼠的心脏功能[J]. 南方医科大学学报, 2025, 45(10): 2062-2070.
[47] Wang, S., Sun, L., Zhu, Z., Liu, J., Ge, W., Li, B. and Wang, B. (2022) Cryptotanshinone Alleviates Myocardial Ischemia and Reperfusion Injury in Rats to Mitigate ER Stress-Dependent Apoptosis by Modulating the JAK1/STAT3 Axis. American Journal of Translational Research, 14, 5024-5039.
[48] Xiao, G., Liu, J., Wang, H., He, S., Liu, J., Fan, G., et al. (2022) CXCR1 and Its Downstream NF-κB Inflammation Signaling Pathway as a Key Target of Guanxinning Injection for Myocardial Ischemia/Reperfusion Injury. Frontiers in Immunology, 13, Article ID: 1007341.
https://doi.org/10.3389/fimmu.2022.1007341
[49] Li, L., Zou, J., Zhou, M., Li, H., Zhou, T., Liu, X., et al. (2024) Phenylsulfate-Induced Oxidative Stress and Mitochondrial Dysfunction in Podocytes Are Ameliorated by Astragaloside IV Activation of the SIRT1/PGC1α/Nrf1 Signaling Pathway. Biomedicine & Pharmacotherapy, 177, Article ID: 117008.
https://doi.org/10.1016/j.biopha.2024.117008
[50] Shen, Q., Fang, J., Guo, H., Su, X., Zhu, B., Yao, X., et al. (2023) Astragaloside IV Attenuates Podocyte Apoptosis through Ameliorating Mitochondrial Dysfunction by Up-Regulated Nrf2-ARE/TFAM Signaling in Diabetic Kidney Disease. Free Radical Biology and Medicine, 203, 45-57.
https://doi.org/10.1016/j.freeradbiomed.2023.03.022
[51] 陈洁琼, 崔鑫婧. 药用植物丹参提取物丹参酮IIA通过激活PGC-1α缓解过度运动心肌损伤[J]. 分子植物育种, 2026, 24(10): 3436-3443.
[52] Liu, Z., Han, X., You, Y., Xin, G., Li, L., Gao, J., et al. (2024) Shuangshen Ningxin Formula Attenuates Cardiac Microvascular Ischemia/Reperfusion Injury through Improving Mitochondrial Function. Journal of Ethnopharmacology, 323, Article ID: 117690.
https://doi.org/10.1016/j.jep.2023.117690
[53] 刘子馨, 辛高杰, 尤越, 等. 基于线粒体分裂融合探讨丹酚酸B保护H9C2细胞OGD/R损伤的作用机制研究[J]. 药学学报, 2024, 59(2): 374-381.
[54] 韩平, 冯俊, 陈华文. 丹参酮IIA对大鼠心肌缺血再灌注后细胞凋亡的机制研究[J]. 中国中医急症, 2016, 25(10): 1844-1846+1873.
[55] Chen, L., Chen, X., Wang, Q., Yang, S., Zhou, H., Ding, L., et al. (2020) Astragaloside IV Derivative (LS-102) Alleviated Myocardial Ischemia Reperfusion Injury by Inhibiting Drp1ser616 Phosphorylation-Mediated Mitochondrial Fission. Frontiers in Pharmacology, 11, Article No. 1083.
https://doi.org/10.3389/fphar.2020.01083
[56] Wu, L., Fan, Z., Gu, L., Liu, J., Cui, Z., Yu, B., et al. (2023) Qishenyiqi Dripping Pill Alleviates Myocardial Ischemia-Induced Ferroptosis via Improving Mitochondrial Dynamical Homeostasis and Biogenesis. Journal of Ethnopharmacology, 308, Article ID: 116282.
https://doi.org/10.1016/j.jep.2023.116282
[57] 聂佩, 顾崇怀, 乔锐, 等. 黄芪甲苷通过调控线粒体自噬抑制血管紧张素II诱导的心肌纤维化[J]. 中药药理与临床, 2025, 41(12): 52-58.
[58] 周湘忠, 杨书凤, 李玉捷, 等. 线粒体自噬探讨5-Fu心肌毒性及黄芪甲苷的干预机制[J]. 分子诊断与治疗杂志, 2023, 15(10): 1791-1795.
[59] 胡贤丹, 尹国幸. 丹参酮IIA调控PINK1/Parkin通路介导的自噬对糖尿病心肌病大鼠心肌损伤的影响[J]. 心脏杂志, 2027(2): 131-137.
[60] Chen, Z., Zhang, M., Xu, Q., Lu, P., Liu, M., Yin, R., et al. (2024) Huangqi-Danshen Decoction Improves Heart Failure by Regulating Pericardial Adipose Tissue Derived Extracellular Vesicular miR-27a-3p to Activate AMPKα2 Mediated Mitophagy. Phytomedicine, 135, Article ID: 156187.
https://doi.org/10.1016/j.phymed.2024.156187
[61] Liu, X., Lu, J., Liu, S., Huang, D., Chen, M., Xiong, G. and Li, S. (2020) Huangqi-Danshen Decoction Alleviates Diabetic Nephropathy in db/db Mice by Inhibiting PINK1/Parkin-Mediated Mitophagy. American Journal of Translational Research, 12, 989-998.
[62] Chen, M., Zhong, G., Liu, M., He, H., Zhou, J., Chen, J., et al. (2023) Integrating Network Analysis and Experimental Validation to Reveal the Mitophagy-Associated Mechanism of Yiqi Huoxue (YQHX) Prescription in the Treatment of Myocardial Ischemia/Reperfusion Injury. Pharmacological Research, 189, Article ID: 106682.
https://doi.org/10.1016/j.phrs.2023.106682
[63] 秀芝, 李铭, 金桃, 等. 黄芪甲苷对心肌缺血保护作用机制的研究进展[J]. 中国老年学杂志, 2026, 46(3): 562-568.
[64] Yuan, Q., Xie, L. and Chen, C. (2022) Astragalus Polysaccharide Protects against Blood-Brain Barrier Damage in MCAO Rats by Inhibiting P2X7R Channel. Journal of Southern Medical University, 42, 1705-1711. (In Chinese)
[65] Lu, C., Day, C.H., Kuo, C., Wang, T., Ho, T., Lai, P., et al. (2022) Calycosin Alleviates H2O2‐Induced Astrocyte Injury by Restricting Oxidative Stress through the Akt/Nrf2/HO-1 Signaling Pathway. Environmental Toxicology, 37, 858-867.
https://doi.org/10.1002/tox.23449
[66] 赵静宇, 陈发慧, 郝亚杰, 等. 丹酚酸B通过调控AMPK介导的铁死亡保护缺氧/复氧诱导的肾小管上皮细胞的损伤[J]. 海南医学院学报, 2024, 30(15): 1147-1155.
[67] 马莉, 刘志超, 高晟玮, 等. 芪参益气滴丸治疗心血管疾病药理作用与临床应用研究进展[J]. 药物评价研究, 2022, 45(4): 780-787.