四种心脏保护药物对小鼠阿霉素诱导的心脏毒性的不同预防作用

陈怡帆; 沈毅辉; 程蕾蕾; 林瑾仪; 张卉; 汪雪君; 许宇辰; 张健; 葛均波

doi:10.19401/j.cnki.1007-3639.2022.10.002

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四种心脏保护药物对小鼠阿霉素诱导的心脏毒性的不同预防作用

专题论著 | 更新时间：2025-12-31

- 四种心脏保护药物对小鼠阿霉素诱导的心脏毒性的不同预防作用
- Different preventive effects of four cardioprotective agents on mice with adriamycin-induced cardiotoxicity
- 中国癌症杂志 2022年32卷第10期页码：936-947
- 作者机构：
  
  1. 复旦大学附属中山医院心内科，上海 200032
  2. 上海市心血管病研究所，上海 200032
  3. 国家放射与治疗临床医学研究中心，上海 200032
  4. 复旦大学附属中山医院心脏超声诊断科，上海 200032
- 作者简介：
  
  [ "陈怡帆（ORCID：0000-0001-9161-8268），博士，E-mail: 21111210020@m.fudan.edu.cn。" ]
- 基金信息：
  
  国家自然科学基金(82170359)
- DOI：10.19401/j.cnki.1007-3639.2022.10.002
  中图分类号： R730.59
- 网络出版：2022-10-30，
- 稿件说明：
移动端阅览
陈怡帆, 沈毅辉, 程蕾蕾, 等. 四种心脏保护药物对小鼠阿霉素诱导的心脏毒性的不同预防作用[J]. 中国癌症杂志, 2022,32(10):936-947.

Yifan CHEN, Yihui SHEN, Leilei CHENG, et al. Different preventive effects of four cardioprotective agents on mice with adriamycin-induced cardiotoxicity[J]. China Oncology, 2022, 32(10): 936-947.
陈怡帆, 沈毅辉, 程蕾蕾, 等. 四种心脏保护药物对小鼠阿霉素诱导的心脏毒性的不同预防作用[J]. 中国癌症杂志, 2022,32(10):936-947. DOI： 10.19401/j.cnki.1007-3639.2022.10.002.

Yifan CHEN, Yihui SHEN, Leilei CHENG, et al. Different preventive effects of four cardioprotective agents on mice with adriamycin-induced cardiotoxicity[J]. China Oncology, 2022, 32(10): 936-947. DOI： 10.19401/j.cnki.1007-3639.2022.10.002.

摘要

背景与目的：

阿霉素又称多柔比星，是一种广泛使用的蒽环类抗肿瘤药物，但以扩张型心肌病和充血性心力衰竭为典型表现的心脏毒性限制了其更为广泛的临床应用。本研究旨在比较高血压、高脂血症和心肌病的常用心脏保护药物贝那普利、阿托伐他汀、沙库巴曲缬沙坦和卡维地洛对阿霉素诱导的心肌病的保护作用并初步探索其潜在机制。

方法：

将成年雄性C57BL/6小鼠分为：生理盐水组、阿霉素组、阿霉素+阿托伐他汀组（atorvastatin）、阿霉素+贝那普利组（benazepril）、阿霉素+沙库巴曲缬沙坦组（sacubitril/valsartan）和阿霉素+卡维地洛组（carvedilol）。除生理盐水组外，予腹膜内注射阿霉素溶液（每周4 mg/kg）共5周，建立阿霉素诱导的体内心肌病模型。各组每日分别予阿托伐他汀10 mg/kg、贝那普利10 mg/kg、沙库巴曲缬沙坦60 mg/kg（沙库巴曲28.8 mg/kg，缬沙坦31.2 mg/kg）和卡维地洛5 mg/kg，以每日每只0.2 mL的剂量灌胃预处理共6周。进行各组二维超声心动图、细胞凋亡、纤维化和炎症等分析。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）检测心肌细胞中总mRNA，采用蛋白质印迹法（Western blot）检测Bax和Bcl-2的表达水平。在4T1乳腺肿瘤细胞接种的BALB/c小鼠中，对以上不同的心脏保护药物进行治疗前后肿瘤体积和质量予以记录，评估心脏保护药物应用对肿瘤生长的影响。

结果：

这些心脏保护药物都有效地抑制了阿霉素引起的左心室功能障碍，改善了阿霉素相关的组织病理损伤，并皆能抑制阿霉素诱导的细胞凋亡和调节Bcl-2和Bax蛋白的表达，减少心肌细胞中阿霉素介导的促炎细胞因子、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）和白细胞介素-6（interleukin-6，IL-6）的积累。与其他3种药物相比，沙库巴曲缬沙坦能显著提高左心室射血分数（left ventricular ejection fraction，LVEF）（65.1%±3.8%

63.5%±4.6%，61.6%±4.1%，62.1%±5.2%，

0.05）和缩短分数（fractional shortening，FS）（34.2%±3.7%、33.9%±3.3%、32.6%±2.8%和33.0%±3.6%，

0.05），减轻心脏纤维化；贝那普利和沙库巴曲缬沙坦在限制心脏大小、心脏与胫骨长度之比（heart weight to tibia length，HW/TL）和保持心肌细胞横截面积（cardiomyocyte cross-sectional area，CSA）方面具有明显的效果；阿托伐他汀兼具中等水平的抗凋亡以及抗炎功效；卡维地洛的抗炎作用为4种药物之首。

结论：

本研究比较了不同药物对阿霉素诱导的心肌病的保护作用并初步探索了潜在机制。未来大规模临床研究可进一步探索患者层面不同心脏保护药物缓解阿霉素诱导的心脏毒性的潜能。

Abstract

Background and purpose:

Adriamycin

also named as doxorubicin

is an effective antineoplastic anthracycline drug used worldwide. However

its cardiotoxicities characterized as dilated cardiomyopathy and congestive heart failure have limited its clinical application. This study aimed to compare the effects of b

enazepril

atorvastatin

sacubitril/valsartan and carvedilol on the protection of adriamycin-induced cardiomyopathy

which are commonly used as cardioprotective agents for hypertension

hyperlipidemia and cardiomyopathy

and then preliminarily explored the underlying mechanisms.

Methods:

Adult male C57BL/6 mice were divided into saline

adriamycin

adriamycin+atorvastatin

adriamycin+benazepril

adriamycin+sacubitril/valsartan and adriamycin+carvedilol groups. In addition to the saline group

adriamycin solution (4 mg/kg per week) was injected intraperitoneally for 5 weeks to establish the dox-induced cardiomyopathy model

in vivo

. Different groups were pretreated with different cardioprotective agents 0.2 mL per day for each mouse by gavage for a total of 6 weeks. The dose was: atorvastatin 10 mg/kg per day

benazepril 10 mg/kg per day

sakubactro/valsartan 60 mg/kg per day (sakubactro 28.8 mg/kg per day

valsartan 31.2 mg/kg per day) and carvedilol 5 mg/kg per day

respectively. Two-dimensional echocardiography

cell apoptosis

fibrosis and inflammation markers were analyzed in these mice. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the total mRNA in cardiomyocytes

and Western blot was used to detect the expression levels of Bax and Bcl-2. Among BALB/c mice inoculated with 4T1 breast tumor cells

the tumor volume and mass were studied before and after treatments with different cardioprotective drugs to evaluate the effects of cardioprotective drugs on tumor growth.

Results:

The data revealed that all these four cardioprotective agents effectively inhibited adriamycin-induced left ventricular dysfunction

ameliorated histopathological damage

suppressed adriamycin-induced cell apoptosis and modulated the expressions of Bcl-2 and Bax proteins. They also attenuated adriamycin-mediated expressions of proinflammatory cytokines

tumor necrosis factor-α (TNF-α)

interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the myocardium.

Furthermore

sacubitril/valsartan not only enormously improved left ventricular ejection fraction (LVEF) (65.1%±3.8%

63.5%±4.6%

61.6%±4.1% and 62.1%±5.2%

0.05) and fractional shortening (FS) (34.2%±3.7%

33.9%±3.3%

32.6%±2.8% and 33.0%±3.6%

0.05)

but also alleviated cardiac fibrosis compared with the other three medicaments. Benazepril and sacubitril/valsartan manifested curative effect in limiting the size of the heart

the ratio of heart weight to tibia length (HW/TL)

and cardiomyocyte cross-sectional area (CSA). Atorvastatin owned a moderate level of anti-apoptotic and anti-inflammatory properties. Among these medications

carvedilol provided the best anti-inflammatory effects.

Conclusion:

We compared different agents for their effects on the protection of adriamycin-induced cardiomyopathy and preliminarily explored underlying mechanisms. In the future

large-scale clinical studies could further explore the potential of different cardioprotective drugs at the patient level to alleviate adriamycin-induced cardiotoxicities.

关键词

Keywords

references

Early Breast Cancer Trialists' Collaborative Group (EBCTCG) . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials [J ] . Lancet , 2005 , 365 ( 9472 ): 1687 - 1717 . DOI: 10.1016/S0140-6736(05)66544-0 http://doi.org/10.1016/S0140-6736(05)66544-0

SINGAL P K , ILISKOVIC N . Doxorubicin-induced cardiomyopathy [J ] . N Engl J Med , 1998 , 339 ( 13 ): 900 - 905 . DOI: 10.1056/NEJM199809243391307 http://doi.org/10.1056/NEJM199809243391307 http://www.nejm.org/doi/abs/10.1056/NEJM199809243391307 http://www.nejm.org/doi/abs/10.1056/NEJM199809243391307

FELKER G M , THOMPSON R E , HARE J M , et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy [J ] . N Engl J Med , 2000 , 342 ( 15 ): 1077 - 1084 . DOI: 10.1056/NEJM200004133421502 http://doi.org/10.1056/NEJM200004133421502 http://www.nejm.org/doi/abs/10.1056/NEJM200004133421502 http://www.nejm.org/doi/abs/10.1056/NEJM200004133421502

MANTAWY E M , EL-BAKLY W M , ESMAT A , et al. Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis [J ] . Eur J Pharmacol , 2014 , 728 : 107 - 118 . DOI: 10.1016/j.ejphar.2014.01.065 http://doi.org/10.1016/j.ejphar.2014.01.065

GUO R M , LIN J C , XU W M , et al. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells [J ] . Int J Mol Med , 2013 , 31 ( 3 ): 644 - 650 . DOI: 10.3892/ijmm.2013.1246 http://doi.org/10.3892/ijmm.2013.1246 https://www.spandidos-publications.com/10.3892/ijmm.2013.1246 https://www.spandidos-publications.com/10.3892/ijmm.2013.1246

GUO R M , WU K , CHEN J F , et al. Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK/NFκB pathway in H9c2 cardiac cells [J ] . Cell Physiol Biochem , 2013 , 32 ( 6 ): 1668 - 1680 . DOI: 10.1159/000356602 http://doi.org/10.1159/000356602

ROCCA C , PASQUA T , CERRA M C , et al. Cardiac damage in anthracyclines therapy: focus on oxidative stress and inflammation [J ] . Antioxid Redox Signal , 2020 , 32 ( 15 ): 1081 - 1097 . DO I: 10.1089/ars.2020.8016 http://doi.org/10.1089/ars.2020.8016 https://www.liebertpub.com/doi/10.1089/ars.2020.8016 https://www.liebertpub.com/doi/10.1089/ars.2020.8016

TIMM K N , TYLER D J . The role of AMPK activation for cardioprotection in doxorubicin-induced cardiotoxicity [J ] . Cardiovasc Drugs Ther , 2020 , 34 ( 2 ): 255 - 269 . DOI: 10.1007/s10557-020-06941-x http://doi.org/10.1007/s10557-020-06941-x

CARDINALE D , COLOMBO A , BACCHIANI G , et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy [J ] . Circulation , 2015 , 131 ( 22 ): 1981 - 1988 . DOI: 10.1161/CIRCULATIONAHA.114.013777 http://doi.org/10.1161/CIRCULATIONAHA.114.013777

ZAMORANO J L , LANCELLOTTI P , RODRIGUEZ MUÑOZ D , et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines [J ] . Eur J Heart Fail , 2017 , 19 ( 1 ): 9 - 42 . DOI: 10.1002/ejhf.654 http://doi.org/10.1002/ejhf.654 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.654 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.654

CHENG J , KAMIYA K , KODAMA I . Carvedilol: molecular and cellular basis for its multifaceted therapeutic potential [J ] . Cardiovasc Drug Rev , 2001 , 19 ( 2 ): 152 - 171 .

DULIN B , ABRAHAM W T . Pharmacology of carvedilol [J ] . Am J Cardiol , 2004 , 93 ( 9 ): 3 - 6 .

GAO G , JIANG S L , GE L L , et al. Atorvastatin improves doxorubicin-induced cardiac dysfunction by modulating Hsp70, Akt, and MAPK signaling pathways [J ] . J Cardiovasc Pharmacol , 2019 , 73 ( 4 ): 223 - 231 . DOI: 10.1097/FJC.0000000000000646 http://doi.org/10.1097/FJC.0000000000000646

MCMURRAY J J , PACKER M , DESAI A S , et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure [J ] . N Engl J Med , 2014 , 371 ( 11 ): 993 - 1004 . DOI: 10.1056/NEJMoa1409077 http://doi.org/10.1056/NEJMoa1409077 http://www.nejm.org/doi/10.1056/NEJMoa1409077 http://www.nejm.org/doi/10.1056/NEJMoa1409077

XIA Y , CHEN Z W , CHEN A , et al. LCZ696 improves cardiac function via alleviating Drp1-mediated mitochondrial dysfunction in mice with doxorubicin-induced dilated cardiomyopathy [J ] . J Mol Cell Cardiol , 2017 , 108 : 138 - 148 . DOI: S0022-2828(17)30113-X http://doi.org/S0022-2828(17)30113-X

PAN J A , TANG Y , YU J Y , et al. miR-146a attenuates apoptosis and modulates autophagy by targeting TAF9b/P53 pathway in doxorubicin-induced cardiotoxicity [J ] . Cell Death Dis , 2019 , 10 ( 9 ): 668 . DOI: 10.1038/s41419-019-1901-x http://doi.org/10.1038/s41419-019-1901-x https://doi.org/10.1038/s41419-019-1901-x https://doi.org/10.1038/s41419-019-1901-x

HULLIN R , MÉTRICH M , SARRE A , et al. Diverging effects of enalapril or eplerenone in primary prevention against doxorubicin-induced cardiotoxicity [J ] . Cardiovasc Res , 2018 , 114 ( 2 ): 272 - 281 . DOI: 10.1093/cvr/cvx162 http://doi.org/10.1093/cvr/cvx162

MUCHIR A , WU W , SERA F , et al. Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin Ⅱ converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation [J ] . Biochem Biophys Res Commun , 2014 , 452 ( 4 ): 958 - 961 . DOI: 10.1016/j.bbrc.2014.09.020 http://doi.org/10.1016/j.bbrc.2014.09.020 https://linkinghub.elsevier.com/retrieve/pii/S0006291X14016283 https://linkinghub.elsevier.com/retrieve/pii/S0006291X14016283

ZHAN D Y , MORIMOTO S , DU C K , et al. Therapeutic effect of{beta}-adrenoceptor blockers using a mouse model of dilated cardiomyopathy with a troponin mutation [J ] . Cardiovasc Res , 2009 , 84 ( 1 ): 64 - 71 . DOI: 10.1093/cvr/cvp168 http://doi.org/10.1093/cvr/cvp168 https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvp168 https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvp168

ZHANG Q L , YANG J J , ZHANG H S . Carvedilol (CAR) combined with carnosic acid (CAA) attenuates doxorubicin-induced cardiotoxicity by suppressing excessive oxidative stress, inflammation, apoptosis and autophagy [J ] . Biomed Pharmacother , 2019 , 109 : 71 - 83 . DOI: 10.1016/j.biopha.2018.07.037 http://doi.org/10.1016/j.biopha.2018.07.037 https://linkinghub.elsevier.com/retrieve/pii/S0753332218307959 https://linkinghub.elsevier.com/retrieve/pii/S0753332218307959

YE Y , GONG H , WANG X X , et al. Combination treatment with antihypertensive agents enhances the effect of qiliqiangxin on chronic pressure overload-induced cardiac hypertrophy and remodeling in male mice [J ] . J Cardiovasc Pharmacol , 2015 , 65 ( 6 ): 628 - 639 . DOI: 10.1097/FJC.0000000000000230 http://doi.org/10.1097/FJC.0000000000000230

LIPSHULTZ S E , SCULLY R E , LIPSITZ S R , et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial [J ] . Lancet Oncol , 2010 , 11 ( 10 ): 950 - 961 . DOI: 10.1016/S1470-2045(10)70204-7 http://doi.org/10.1016/S1470-2045(10)70204-7

LI M C , SALA V , DE SANTIS M C , et al. Phosphoinositide 3-kinase gamma inhibition protects from anthracycline cardiotoxicity and reduces tumor growth [J ] . Circulation , 2018 , 138 ( 7 ): 696 - 711 . DOI: 10.1161/CIRCULATIONAHA.117.030352 http://doi.org/10.1161/CIRCULATIONAHA.117.030352

PACKER M , MCMURRAY J J , DESAI A S , et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure [J ] . Circulation , 2015 , 131 ( 1 ): 54 - 61 . DOI: 10.1161/CIRCULATIONAHA.114.013748 http://doi.org/10.1161/CIRCULATIONAHA.114.013748

LEVIN E R , GARDNER D G , SAMSON W K . Natriuretic peptides [J ] . N Engl J Med , 1998 , 339 ( 5 ): 321 - 328 . DOI: 10.1056/NEJM199807303390507 http://doi.org/10.1056/NEJM199807303390507 http://www.nejm.org/doi/abs/10.1056/NEJM199807303390507 http://www.nejm.org/doi/abs/10.1056/NEJM199807303390507

MOERTL D , BERGER R , STRUCK J , et al. Comparison of midregional pro-atrial and B-type natriuretic peptides in chronic heart failure: influencing factors, detection of left ventricular systolic dysfunction, and prediction of death [J ] . J Am Coll Cardiol , 2009 , 53 ( 19 ): 1783 - 1790 . DOI: 10.1016/j.jacc.2009.01.057 http://doi.org/10.1016/j.jacc.2009.01.057

PONIKOWSKI P , VOORS A A , ANKER S D , et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC [J ] . Eur Heart J , 2016 , 37 ( 27 ): 2129 - 2200 . DOI: 10.1093/eurheartj/ehw128 http://doi.org/10.1093/eurheartj/ehw128 https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehw128 https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehw128

ZHANG Y S , KNIGHT W , CHEN S , et al. Multiprotein complex with TRPC (transient receptor potential-canonical) channel, PDE1C (phosphodiesterase 1C), and A2R (adenosine A2 receptor) plays a critical role in regulating cardiomyocyte cAMP and survival [J ] . Circulation , 2018 , 138 ( 18 ): 1988 - 2002 . DOI: 10.1161/CIRCULATIONAHA.118.034189 http://doi.org/10.1161/CIRCULATIONAHA.118.034189

INSEL J , MIRVIS D M , BOLAND M J , et al. A multicenter study of the safety and efficacy of benazepril hydrochloride, a long-acting angiotensin-converting enzyme inhibitor, in patients with chronic congestive heart failure [J ] . Clin Pharmacol Ther , 1989 , 45 ( 3 ): 312 - 320 .

COLLABORATION A R B T . Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals [J ] . J Hypertens , 2011 , 29 ( 4 ): 623 - 635 . DOI: 10.1097/HJH.0b013e328344a7de http://doi.org/10.1097/HJH.0b013e328344a7de https://journals.lww.com/00004872-201104000-00001 https://journals.lww.com/00004872-201104000-00001

HO C Y , DAY S M , AXELSSON A , et al. Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial [J ] . Nat Med , 2021 , 27 ( 10 ): 1818 - 1824 . DOI: 10.1038/s41591-021-01505-4 http://doi.org/10.1038/s41591-021-01505-4

RURIK J G , TOMBÁCZ I , YADEGARI A , et al. CAR T cells produced in vivo to treat cardiac injury [J ] . Science , 2022 , 375 ( 6576 ): 91 - 96 . DOI: 10.1126/science.abm0594 http://doi.org/10.1126/science.abm0594 https://www.science.org/doi/10.1126/science.abm0594 https://www.science.org/doi/10.1126/science.abm0594

DESAI A S , MCMURRAY J J , PACKER M , et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients [J ] . Eur Heart J , 2015 , 36 ( 30 ): 1990 - 1997 . DOI: 10.1093/eurheartj/ehv186 http://doi.org/10.1093/eurheartj/ehv186

GE Q , ZHAO L , REN X M , et al. LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates diabetic cardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis [J ] . Exp Biol Med (Maywood) , 2019 , 244 ( 12 ): 1028 - 1039 . DOI: 10.1177/1535370219861283 http://doi.org/10.1177/1535370219861283

MIZUTA Y , TOKUDA K , GUO J , et al. Sodium thiosulfate prevents doxorubicin-induced DNA damage and apoptosis in cardiomyocytes in mice [J ] . Life Sci , 2020 , 257 : 118074 . DOI: 10.1016/j.lfs.2020.118074 http://doi.org/10.1016/j.lfs.2020.118074 https://linkinghub.elsevier.com/retrieve/pii/S0024320520308250 https://linkinghub.elsevier.com/retrieve/pii/S0024320520308250

CHILDS A C , PHANEUF S L , DIRKS A J , et al. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2: Bax ratio [J ] . Cancer Res , 2002 , 62 ( 16 ): 4592 - 4598 .

MALEK V , GAIKWAD A B . Telmisartan and thiorphan combination treatment attenuates fibrosis and apoptosis in preventing diabetic cardiomyopathy [J ] . Cardiovasc Res , 2018 , 115 ( 2 ): 373 - 384 . DOI: 10.1093/cvr/cvy226 http://doi.org/10.1093/cvr/cvy226 https://academic.oup.com/cardiovascres/article/115/2/373/5090455 https://academic.oup.com/cardiovascres/article/115/2/373/5090455

SABBAH H N . Silent disease progression in clinically stable heart failure [J ] . Eur J Heart Fail , 2017 , 19 ( 4 ): 469 - 478 . DOI: 10.1002/ejhf.705 http://doi.org/10.1002/ejhf.705

JIA W K , BAI T , ZENG J , et al. Combined administration of metformin and atorvastatin attenuates diabetic cardiomyopathy by inhibiting inflammation, apoptosis, and oxidative stress in type 2 diabetic mice [J ] . Front Cell Dev Biol , 2021 , 9 : 634900 . DOI: 10.3389/fcell.2021.634900 http://doi.org/10.3389/fcell.2021.634900 https://www.frontiersin.org/articles/10.3389/fcell.2021.634900/full https://www.frontiersin.org/articles/10.3389/fcell.2021.634900/full

WANG Z Q , CHEN M T , ZHANG R , et al. Docosahexaenoic acid attenuates doxorubicin-induced cytotoxicity and inflammation by suppressing NF-κB/iNOS/NO signaling pathway activation in H9C2 cardiac cells [J ] . J Cardiovasc Pharmacol , 2016 , 67 ( 4 ): 283 - 289 . DOI: 10.1097/FJC.0000000000000350 http://doi.org/10.1097/FJC.0000000000000350 http://journals.lww.com/00005344-201604000-00002 http://journals.lww.com/00005344-201604000-00002

WANG Y B , LIU L . Effects of carvedilol on myocardial remodeling, oxidative stress, inflammation indexes and endothelial function in hypertensive rats [J ] . Minerva Surg , 2021 .

ALANAZI A M , FADDA L , ALHUSAINI A , et al. Liposomal resveratrol and/or carvedilol attenuate doxorubicin-induced cardiotoxicity by modulating inflammation, oxidative stress and S100A1 in rats [J ] . Antioxidants (Basel) , 2020 , 9 ( 2 ): E159 .

BANGALORE S , KUMAR S , KJELDSEN S E , et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials [J ] . Lancet Oncol , 2011 , 12 ( 1 ): 65 - 82 . DOI: 10.1016/S1470-2045(10)70260-6 http://doi.org/10.1016/S1470-2045(10)70260-6 https://linkinghub.elsevier.com/retrieve/pii/S1470204510702606 https://linkinghub.elsevier.com/retrieve/pii/S1470204510702606

KEATING G M , JARVIS B . Carvedilol: a review of its use in chronic heart failure [J ] . Drugs , 2003 , 63 ( 16 ): 1697 - 1741 .

SIPAHI I , DEBANNE S M , ROWLAND D Y , et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials [J ] . Lancet Oncol , 2010 , 11 ( 7 ): 627 - 636 . DOI: 10.1016/S1470-2045(10)70106-6 http://doi.org/10.1016/S1470-2045(10)70106-6

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