海南医科大学学报2026，Vol.32Issue(13)：1012-1023,12.DOI:10.13210/j.cnki.jhmu.20250519.002
人参-丹参-黄芪防治阿霉素所致心脏毒性的作用机制研究
Mechanistic study on renshen-danshen-huangqi combination in preventing doxorubicin-induced cardiotoxicity
摘要
Abstract
Objective:To investigate the cardioprotective effects and molecular mechanisms of Renshen-Danshen-Huangqi(RDH)combination against doxorubicin(DOX)-induced cardiotoxicity using network pharmacology,in vitro cell experiments,and in vivo animal studies.Methods:Active components and target proteins of RDH were retrieved from the TCMSP and Uniport databases,while DOX-related cardiotoxicity targets were obtained from GeneCards and OMIM.Common targets were identified using the Venny online platform,and a protein-protein interaction(PPI)network was constructed via the STRING database and visualized using Cytoscape to identify core targets.GO and KEGG pathway enrichment analyses were performed using Metascape.For in vitro experiments,H9c2 cardiomyocytes were treated with DOX for 24 h to establish a myocardial injury model.The opti-mal RDH ratio was determined via MTT assay,and its effect on cell viability and apoptosis(flow cytometry)was evaluated.For in vivo studies,a DOX-induced cardiotoxicity model was established in SD rats via intraperitoneal injection.Cardiac function(echocardiography:LVDD,LVDS,LVEF,LVFS),histopathology(H&E and Masson staining),serum biomarkers(Tn-I,CK-MB,MDA,GSH,SOD,GSH-PX),and apoptosis-related proteins(BCL2,BAX,Cleaved-caspase3;Western blot)were analyzed.Results:Network pharmacology analysis identified 154 potential therapeutic targets of RDH(including BCL2 and Cas-pase3)for DOX-induced cardiotoxicity,involving 20 key pathways such as the apoptosis signaling pathway.In vitro experiments demonstrated that the RDH combination at a ratio of 1∶2∶1(Renshen∶Danshen∶Huangqi)most effectively restored DOX-induced cardiomyocyte damage and significantly attenuated DOX-triggered apoptosis(P<0.05).In vivo studies revealed that RDH admin-istration significantly alleviated DOX-induced cardiac dysfunction and oxidative stress in rats,while effectively improving patholog-ical damage in heart tissue(P<0.05).Notably,RDH significantly upregulated myocardial BCL2 protein expression while down-regulating pro-apoptotic proteins BAX and Cleaved-Caspase3(P<0.05).Conclusion:RDH significantly attenuates DOX-induced cardiotoxicity,potentially via anti-apoptotic,antioxidant,and modulation of Caspase3/BCL2.关键词
阿霉素/心脏毒性/人参-丹参-黄芪(RDH)/细胞凋亡/网络药理学Key words
Doxorubicin/Cardiotoxicity/Renshen-Danshen-Huangqi(RDH)/Apoptosis/Network pharmacology分类
医药卫生引用本文复制引用
李梓慕,王斯琦,杨丽丽,杨文,王娟,张琳,刘东玲..人参-丹参-黄芪防治阿霉素所致心脏毒性的作用机制研究[J].海南医科大学学报,2026,32(13):1012-1023,12.基金项目
This study was supported by the 2023 Annual"Western Young Scholars"(23JR6KA028) （23JR6KA028）
2023 National Natural Science Foundation Project(82360790) （82360790）
2023 Outstanding Young Scholars Fund Project(23JRRA1203) 2023年度"西部青年学者"(23JR6KA028) （23JRRA1203）
2023年国家自然科学基金项目(82360790) （82360790）
2023年度杰出青年基金项目(23JR-RA1203) （23JR-RA1203）
