Research Progress on Adriamycin-Induced Myocardial Injury: Pathological Mechanism and Animal Model

Xuanyi TAO, Fangfang XU, Qirui SHEN, Yuxin CHEN, Hui FU

Acta Academiae Medicinae Sinicae ›› 2026, Vol. 48 ›› Issue (1) : 170-176.

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Acta Academiae Medicinae Sinicae

Abbreviation (ISO4): Acta Academiae Medicinae Sinicae      Editor in chief: Xuetao CAO

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Acta Academiae Medicinae Sinicae ›› 2026, Vol. 48 ›› Issue (1) : 170-176. DOI: 10.3881/j.issn.1000-503X.16565
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Research Progress on Adriamycin-Induced Myocardial Injury: Pathological Mechanism and Animal Model

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Abstract

Adriamycin is an anthracycline chemotherapy drug used in cancer treatment,and its cardiotoxicity primarily manifests as structural and functional damage to myocardial cells,which can lead to severe cardiovascular diseases such as heart failure.This article reviews recent advances in adriamycin-induced myocardial injury,focusing on its pathological mechanisms,potential therapeutic drugs,and commonly used animal models,to provide a research basis and intervention strategies for developing effective treatments.

Key words

adriamycin / myocardial injury / pathological feature / current therapies / animal model

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Xuanyi TAO , Fangfang XU , Qirui SHEN , et al . Research Progress on Adriamycin-Induced Myocardial Injury: Pathological Mechanism and Animal Model[J]. Acta Academiae Medicinae Sinicae. 2026, 48(1): 170-176 https://doi.org/10.3881/j.issn.1000-503X.16565

References

[1]
田欣, 姬林娟, 高旺, 等. 中医药介导的铁死亡在阿霉素所致心脏毒性中的作用机制[J]. 生命的化学, 2024, 44(5):884-889.DOI:10.13488/j.smhx.20230933.
[2]
Zhang H, Xu A, Sun X, et al. Self-maintenance of cardiac resident reparative macrophages attenuates doxorubicin-induced cardiomyopathy through the SR-A1-c-Myc axis[J]. Circ Res, 2020, 127(5):610-627.DOI:10.1161/CIRCRESAHA.119.316428.
[3]
Zhang Y, Ni L, Lin B, et al. SNX17 protects the heart from doxorubicin-induced cardiotoxicity by modulating LMOD2 degradation[J]. Pharmacol Res, 2021, 169:105642.DOI:10.1016/j.phrs.2021.105642.
[4]
Li D, Yang Y, Wang S, et al. Role of acetylation in doxorubicin-induced cardiotoxicity[J]. Redox Biol, 2021, 46:102089.DOI:10.1016/j.redox.2021.102089.
[5]
Shati AA, El-Kott AF. Acylated ghrelin prevents doxorubicin-induced cardiac intrinsic cell death and fibrosis in rats by restoring IL-6/JAK2/STAT3 signaling pathway and inhibition of STAT1[J]. Naunyn Schmiedebergs Arch Pharmacol, 2019, 392(9):1151-1168.DOI:10.1007/s00210-019-01664-9.
[6]
Whelan RS, Konstantinidis K, Wei AC, et al. Bax regulates primary necrosis through mitochondrial dynamics[J]. Proc Natl Acad Sci U S A, 2012, 109(17):6566-6571.DOI:10.1073/pnas.1201608109.
[7]
Xie L, Xue F, Cheng C, et al. Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy via inhibiting TNFα-TRAF3-TAK1-MAPK axis[J]. Signal Transduct Target Ther, 2024, 9(1):273.DOI:10.1038/s41392-024-01977-z.
[8]
耿洁, 刘洁婕, 刘亚, 等. 上调miR-21-5p对阿霉素诱导的心肌细胞增殖、凋亡的影响及其机制研究[J]. 广西医科大学学报, 2024, 41(5):722-727.DOI:10.16190/j.cnki.45-1211/r.2024.05.012.
[9]
Chen S, Chen J, Du W, et al. PDE10A inactivation prevents doxorubicin-induced cardiotoxicity and tumor growth[J]. Circ Res, 2023, 133(2):138-157.DOI:10.1161/CIRCRESAHA.122.322264.
[10]
Yu P, Zhang X, Liu N, et al. Pyroptosis:mechanisms and diseases[J]. Signal Transduct Target Ther, 2021, 6(1):128.DOI:10.1038/s41392-021-00507-5.
[11]
Zeng C, Duan F, Hu J, et al. NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy[J]. Redox Biol, 2020, 34:101523.DOI:10.1016/j.redox.2020.101523.
[12]
Wei X, Xie F, Zhou X, et al. Role of pyroptosis in inflammation and cancer[J]. Cell Mol Immunol, 2022, 19(9):971-992.DOI:10.1038/s41423-022-00905-x.
[13]
Zhong Z, Gao Y, Zhou J, et al. Inhibiting mir-34a-5p regulates doxorubicin-induced autophagy disorder and alleviates myocardial pyroptosis by targeting Sirt3-AMPK pathway[J]. Biomed Pharmacother, 2023, 168:115654.DOI:10.1016/j.biopha.2023.115654.
[14]
施佳君, 杨钦钦, 富丹婷, 等. 冠心宁片抑制NLRP3/ASC/Caspase-1通路改善阿霉素诱导的扩张型心肌病大鼠心肌细胞焦亡[J]. 中国实验动物学报, 2024, 32(3):337-346.DOI:10.3969/j.issn.1005-4847.2024.03.007.
[15]
熊凤梅, 刘瑞萍, 李洋, 等. 和厚朴酚可体外减轻阿霉素诱导的心肌毒性:基于激活 AMPK/Nrf2 信号通路抑制细胞焦亡[J]. 南方医科大学学报, 2022, 42(8):1205-1211.DOI:10.12122/j.issn.1673-4254.2022.08.13.
[16]
Xiao B, Hong L, Cai X, et al. The true colors of autophagy in doxorubicin induced cardiotoxicity[J]. Oncol Lett, 2019, 18(3):2165-2172.DOI:10.3892/ol.2019.10576.
[17]
Peng K, Zeng C, Gao Y, et al. Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling[J]. Acta Pharm Sin B, 2023, 13(6):2680-2700.DOI:10.1016/j.apsb.2023.03.019.
[18]
Nakagama S, Maejima Y, Fan Q, et al. Endoplasmic reticulum selective autophagy alleviates anthracycline-induced cardiotoxicity[J]. JACC CardioOncol, 2023, 5(5):656-670.DOI:10.1016/j.jaccao.2023.05.009.
[19]
Pan JA, Zhang H, Lin H, et al. Irisin ameliorates doxorubicin-induced cardiac perivascular fibrosis through inhibiting endothelial-to-mesenchymal transition by regulating ROS accumulation and autophagy disorder in endothelial cells[J]. Redox Biol, 2021, 46:102120.DOI:10.1016/j.redox.2021.102120.
[20]
Yi X, Wang Q, Zhang M, et al. Ferroptosis:a novel therapeutic target of natural products against doxorubicin-induced cardiotoxicity[J]. Biomed Pharmacother, 2024, 178:117217.DOI:10.1016/j.biopha.2024.117217.
[21]
Yu W, Hu Y, Liu Z, et al. Sorting nexin 3 exacerbates doxorubicin-induced cardiomyopathy via regulation of TFRC-dependent ferroptosis[J]. Acta Pharm Sin B, 2023, 13(12):4875-4892.DOI:10.1016/j.apsb.2023.08.016.
[22]
Qiu H, Huang S, Liu Y, et al. Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis[J]. Acta Pharm Sin B, 2024, 14(6):2581-2597.DOI:10.1016/j.apsb.2024.03.015.E.
[23]
Huang C, Guo Y, Li T, et al. Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy[J]. Redox Biol, 2024, 70:103024.DOI:10.1016/j.redox.2023.103024.
[24]
Wu L, Du Y, Wang L, et al. Inhibition of METTL3 ameliorates doxorubicin-induced cardiotoxicity through suppression of TFRC-mediated ferroptosis[J]. Redox Biol, 2024, 72:103157.DOI:10.1016/j.redox.2024.103157.
[25]
Cui J, Chen Y, Yang Q, et al. Protosappanin A protects DOX-induced myocardial injury and cardiac dysfunction by targeting ACSL4/FTH1 axis-dependent ferroptosis[J]. Adv Sci(Weinh), 2024, 11(34):e2310227.DOI:10.1002/advs.202310227.
[26]
Luo W, Zou X, Wang Y, et al. Critical role of the cGAS-STING pathway in doxorubicin-induced cardiotoxicity[J]. Circ Res, 2023, 132(11):e223-e242.DOI:10.1161/CIRCRESAHA.122.321587.
[27]
李润琦, 翟志红, 杜晴晴, 等. TBHQ对阿霉素慢性心脏毒性大鼠的保护作用[J]. 山西医科大学学报, 2024, 55(7):835-841.DOI:10.13753/j.issn.1007-6611.2024.07.004.
[28]
Dabour MS, Abdelgawad IY, Sadaf B, et al. Losmapimod ameliorates doxorubicin-induced cardiotoxicity through attenuating senescence and inflammatory pathways[J]. Biomed Pharmacother, 2024, 179:117288.DOI:10.1016/j.biopha.2024.117288.
[29]
Alwaili MA, Abu-Almakarem AS, El-Said KS, et al. Shikimic acid protects against doxorubicin-induced cardiotoxicity in rats[J]. Sci Rep, 2025, 15(1):8126.DOI:10.1038/s41598-025-90549-4.
[30]
Chen C, Jiang L, Zhang M, et al. Isodunnianol alleviates doxorubicin-induced myocardial injury by activating protective autophagy[J]. Food Funct, 2019, 10(5):2651-2657.DOI:10.1039/c9fo00063a.
[31]
Cheng Y, Wu X, Nie X, et al. Natural compound glycyrrhetinic acid protects against doxorubicin-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway[J]. Phytomedicine, 2022, 106:154407.DOI:10.1016/j.phymed.2022.154407.
[32]
陈鹏, 刘石琳, 朱小蕾, 等. 基于FGF2表达探讨红景天苷对阿霉素诱导的心脏毒性的保护作用及对NLRP3炎症小体的影响[J]. 现代中西医结合杂志, 2024, 33(13):1794-1800,1806.DOI:10.3969/j.issn.1008-8849.2024.13.008.
[33]
李银萍, 宣悦, 廖玮嫣, 等. 葛根素通过AMPK/ASMase激活自噬减轻阿霉素诱导的心肌细胞毒性[J]. 中药新药与临床药理, 2024, 35(10):1520-1530.DOI:10.19378/j.issn.1003-9783.2024.10.009.
[34]
陈榕榕, 郑平, 李得清, 等. 益气化瘀汤调控miR-532-3p改善阿霉素心脏毒性的机制研究[J]. 中国中医药信息杂志, 2025, 32(1):128-133.DOI:10.19879/j.cnki.1005-5304.202403652.
[35]
Kanwal U, Irfan Bukhari N, Ovais M, et al. Advances in nano-delivery systems for doxorubicin:an updated insight[J]. J Drug Target, 2018, 26(4):296-310.DOI:10.1080/1061186X.2017.1380655.
[36]
彭凤丽, 李朝富, 石蓓. 纳米囊泡递送系统在心血管疾病中的应用[J]. 中国组织工程研究, 2023, 27(30):4862-4868.DOI:10.12307/2023.470.
[37]
Yarana C, Siwaponanan P, Maneechote C, et al. Extracellular vesicles released after doxorubicin treatment in rats protect cardiomyocytes from oxidative damage and induce pro-inflammatory gene expression in macrophages[J]. Int J Mol Sci, 2022, 23(21):13465.DOI:10.3390/ijms232113465.
[38]
O’Brien CG, Ozen MO, Ikeda G, et al. Mitochondria-rich extracellular vesicles rescue patient-specific cardiomyocytes from doxorubicin injury:insights into the SENECA trial[J]. JACC CardioOncol, 2021, 3(3):428-440.DOI:10.1016/j.jaccao.2021.05.006.
[39]
Beaumier A, Robinson SR, Robinson N, et al. Extracellular vesicular microRNAs as potential biomarker for early detection of doxorubicin-induced cardiotoxicity[J]. J Vet Intern Med, 2020, 34(3):1260-1271.DOI:10.1111/jvim.15762.
[40]
赵荫涛, 杨莹莹, 张相钦, 等. 卵泡抑素样蛋白1对阿霉素所致小鼠急性心肌损伤的改善作用及其机制[J]. 吉林大学学报(医学版), 2023, 49(3):565-572.DOI:10.13481/j.1671-587X.20230303.
[41]
卢维哲, 刘海琼, 杨涵滟, 等. MG53蛋白对小鼠阿霉素急性心肌毒性的影响及机制[J]. 中山大学学报(医学科学版), 2023, 44(1):34-43.DOI:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20221208.001.
[42]
Sheibani M, Nezamoleslami S, Faghir-Ghanesefat H, et al. Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats[J]. Cancer Chemother Pharmacol, 2020, 85(3):563-571.DOI:10.1007/s00280-019-04019-6.
[43]
Eisvand F, Imenshahidi M, Ghasemzadeh Rahbardar M, et al. Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats[J]. Phytother Res, 2022, 36(1):506-524.DOI:10.1002/ptr.7356.
[44]
de Barros JC, Pereira AG, Rodrigues MA, et al. Effects of omega 3 on doxorubicin-induced cardiotoxicity in an experimental rabbit model[J]. Res Socie Devel, 2021, 10:e60101320993.DOI:10.33448/rsd-v10i13.20993.
[45]
Ge W, Zhang X, Lin J, et al. Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner[J]. Cell Death Dis, 2025, 16(1):2.DOI:10.1038/s41419-024-07322-0.
[46]
Wu L, Wang LT, Du YX, et al. Asiatic acid ameliorates doxorubicin-induced cardiotoxicity by promoting FPN-mediated iron export and inhibiting ferroptosis[J]. Acta Pharmacol Sin, 2025, 46(1):81-95.DOI:10.1038/s41401-024-01367-9.
[47]
Kuno A, Hosoda R, Tsukamoto M, et al. SIRT1 in the cardiomyocyte counteracts doxorubicin-induced cardiotoxicity via regulating histone H2AX[J]. Cardiovasc Res, 2023, 118(17):3360-3373.DOI:10.1093/cvr/cvac026.
[48]
Qaed E, Almoiliqy M, Liu W, et al. Protective effects of phosphocreatine against Doxorubicin-Induced cardiotoxicity through mitochondrial function enhancement and apoptosis suppression via AMPK/PGC-1α signaling pathway[J]. Int Immunopharmacol, 2025, 144:113677.DOI:10.1016/j.intimp.2024.113677.
[49]
He ML, Li XY, Guo YQ, et al. Nerol attenuates doxorubicin-induced heart failure by inhibiting cardiomyocyte apoptosis in rats[J]. Eur J Pharmacol, 2025, 987:177203.DOI:10.1016/j.ejphar.2024.177203.
[50]
Romão PVM, Palozi RAC, Guarnier LP, et al. Cardioprotective effects of Plinia cauliflora(Mart.)Kausel in a rabbit model of doxorubicin-induced heart failure[J]. J Ethnopharmacol, 2019, 242:112042.DOI:10.1016/j.jep.2019.112042.
[51]
张冬, 朱瑾彦, 张敏, 等. 扩张型心肌病动物模型的建立与评估[J]. 实验动物科学, 2023, 40(4):55-61.DOI:10.3969/j.issn.1006-6179.2023.04.011.

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