中国临床医学2026，Vol.33Issue(4)：582-591,10.DOI:10.12025/j.issn.1008-6358.2026.20260058
HydroMg通过减轻氧化应激与改善线粒体功能缓解阿霉素慢性心脏毒性
HydroMg alleviates doxorubicin-induced chronic cardiotoxicity by attenuating oxidative stress and improving mitochondrial function
摘要
Abstract
Objective To investigate the protective effect and underlying mechanisms of HydroMg,a novel sustained-release hydrogen donor,in a model of doxorubicin(DOX)-induced chronic cardiotoxicity.Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg,and mitochondrial membrane potential,reactive oxygen species(ROS)levels,and apoptosis were measured.In the animal experiment,mice were divided into control,HydroMg,DOX,and DOX+HydroMg groups.The HydroMg group received intraperitoneal injection of HydroMg(100 mg/kg).Chronic cardiotoxicity was established by intraperitoneal injection of DOX(5 mg/kg every week)for four consecutive weeks;In the DOX+HydroMg group,HydroMg(100 mg/kg)was administered intraperitoneally 4-5 h prior to each DOX injection.Cardiac function and remodeling were evaluated by echocardiography and heart weight index(HWI).The long-term survival of mice were analyzed.Subsequently,transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls.Results At the cellular level,HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress,as evidenced by restored membrane potential,reductions in total ROS and mitochondrial superoxide levels by approximately 30%and 9%,respectively,and a decrease in the apoptosis rate from 34.13%to 18.27%.In the animal model,compared with the DOX group,HydroMg intervention increased left ventricular ejection fraction(LVEF)and fractional shortening(LVFS)by 9.62%and 5.82%,respectively,attenuated the reduction in HWI(4.41 mg/mm vs 3.53 mg/mm),and improved the 4-week survival rate(80%vs 60%).Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity,including widespread suppression of oxidative phosphorylation and antioxidant pathways.Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function,and provides a potential therapeutic strategy against DOX-related cardiotoxicity.关键词
HydroMg/阿霉素/慢性心脏毒性/氧化应激/线粒体功能Key words
HydroMg/doxorubicin/chronic cardiotoxicity/oxidative stress/mitochondrial function分类
医药卫生引用本文复制引用
张露,丁之光,孙晓垒,张春晓,安健,马秀瑞,金亚伟,张育宁,高雄,李莫涵,袁泽,陆逸华,丁文江..HydroMg通过减轻氧化应激与改善线粒体功能缓解阿霉素慢性心脏毒性[J].中国临床医学,2026,33(4):582-591,10.基金项目
国家自然科学基金(82270264),山西省重点医学研发专项(2021XM30),山西省基础研究计划自由探索类项目(202103021223451),山西省卫生健康委员会科研项目(2022028).Supported by National Natural Science Foundation of China(82270264),Shanxi Province Key Medical Research and Development Special Project(2021XM30),Shanxi Provincial Basic Research Program-Free Exploration Category(202103021223451),and Program of Health Commission of Shanxi Province(2022028). （82270264）
