Hui Hui, Du Mingliang, Sun Shize, Sun Lili, He Junying, Li Xue, Jiang Miao, Yu Qin
Dalian Medical University, Dalian, Liaoning 116044, China; Central Hospital of Dalian University of Technology (Dalian Municipal Central Hospital), Dalian, Liaoning 116033, China.
Central Hospital of Dalian University of Technology (Dalian Municipal Central Hospital), Dalian, Liaoning 116033, China.
Int Immunopharmacol. 2025 Aug 1;163:115270. doi: 10.1016/j.intimp.2025.115270.
Acute myocardial infarction (MI) is among the diseases with the highest incidences and seriously threatens public health worldwide, with the present clinical treatment methods presenting considerable risks. Ferroptosis, characterized by iron dependence and intracellular oxidative accumulation, is a type of programmed cell death that has opened new avenues for treating MI. Muscone is one of the major active monomers of musk, which can improve ventricular remodeling after MI and myocardial ischemia-reperfusion injury. However, the ferroptosis mechanism underlying muscone-mediated MI treatment remains unelucidated. Therefore, this study aimed to investigate the mechanisms of action of muscone in MI management both in vivo and in vitro. Notably, muscone could attenuate MI injury, increase myocardial angiogenesis, and inhibit myocardial ferroptosis in the in vivo rat model. Furthermore, in vitro experiment results in rat cardiomyocytes H9c2 cells showed that muscone could inhibit hypoxia-induced cell damage, improve cell viability, and inhibit cell apoptosis and ferroptosis. Mechanistically, muscone-mediated ferroptosis inhibition was regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/System Xc-/glutathione peroxidase 4 (GPX4) signaling pathway to treat MI. Altogether, the results of this study show the therapeutic potential of muscone in MI treatment. These findings provide notable insights regarding the development of therapeutic approaches targeted at the Nrf2/System Xc- /GPX4 signaling pathway.
急性心肌梗死（MI）是发病率最高的疾病之一，严重威胁全球公众健康，目前的临床治疗方法存在相当大的风险。铁死亡是一种程序性细胞死亡，其特征为铁依赖性和细胞内氧化积累，为MI的治疗开辟了新途径。麝香酮是麝香的主要活性单体之一，可改善MI后的心室重塑和心肌缺血再灌注损伤。然而，麝香酮介导MI治疗的铁死亡机制仍未阐明。因此，本研究旨在探讨麝香酮在体内和体外对MI治疗的作用机制。值得注意的是，在体内大鼠模型中，麝香酮可减轻MI损伤，增加心肌血管生成，并抑制心肌铁死亡。此外，在大鼠心肌细胞H9c2细胞中的体外实验结果表明，麝香酮可抑制缺氧诱导的细胞损伤，提高细胞活力，并抑制细胞凋亡和铁死亡。从机制上讲，麝香酮介导的铁死亡抑制是通过核因子红细胞2相关因子2（Nrf2）/系统Xc-/谷胱甘肽过氧化物酶4（GPX4）信号通路来治疗MI的。总之，本研究结果显示了麝香酮在MI治疗中的治疗潜力。这些发现为针对Nrf2/系统Xc-/GPX4信号通路的治疗方法的开发提供了重要见解。
