上海交通大学学报（医学版）2025，Vol.45Issue(12)：1636-1643,8.DOI:10.3969/j.issn.1674-8115.2025.12.009
心力衰竭代谢调节药物的研究进展
Advances in metabolic modulators as therapeutic agents for heart failure
摘要
Abstract
Heart failure is a complex clinical syndrome resulting from structural and functional impairments of the heart,leading to diminished cardiac output and an inability to fulfill the body's metabolic requirements.Perturbations in myocardial energy metabolism represent a central hallmark of heart failure,characterized by altered substrate utilization,mitochondrial dysfunction,and elevated oxidative stress,all of which contribute critically to disease progression.Given the fundamental role of metabolic homeostasis in sustaining cardiac performance,pharmacological agents that target metabolic pathways,collectively termed metabolic modulators,have gained prominence as promising therapeutic strategies for heart failure.For instance,fatty acid oxidation inhibitors such as perhexiline act by suppressing carnitine palmitoyltransferase Ⅰ/Ⅱ(CPT1/2),thereby reducing fatty acid β-oxidation and improving the efficiency of cardiac energy metabolism.Similarly,3-ketoacyl-coenzyme A thiolase(3-KAT)inhibitors,such as trimetazidine,enhance glucose oxidation,thereby improving myocardial energy supply.Sodium-glucose cotransporter 2(SGLT2)inhibitors(e.g.,empagliflozin)not only exert hypoglycemic effects but also confer cardioprotective benefits through pleiotropic mechanisms,although their detailed metabolic actions remain under investigation.Furthermore,mitochondrial-targeting peptides,such as elamipretide,preserve mitochondrial integrity and function by stabilizating cardiolipin,thereby providing additional cardioprotection.Although several metabolic modulators have demonstrated encouraging results in preclinical and early clinical studies,their long-term efficacy and safety profiles await validation in large-scale randomized trials.This review synthesizes recent advances in the development of metabolic modulators for heart failure,providing insights into basic research and the translation of clinical treatments.关键词
心力衰竭/能量代谢/线粒体/药物治疗Key words
heart failure/energy metabolism/mitochondria/pharmacotherapy分类
医药卫生引用本文复制引用
杜泰来,黄展鹏..心力衰竭代谢调节药物的研究进展[J].上海交通大学学报（医学版）,2025,45(12):1636-1643,8.基金项目
国家重点研发计划(2021YFA1302500) （2021YFA1302500）
国家自然科学基金(U23A20396,82270252). National Key Research and Development Program of China(2021YFA1302500) （U23A20396,82270252）
National Natural Science Foundation of China(U23A20396,82270252). （U23A20396,82270252）
