Lin Duomao, Cui Boqun, Qi Zeyou, Liu Wenjun, Zhang Guanzheng
Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Beijing, 100029, People's Republic of China.
J Cardiovasc Transl Res. 2023 Dec;16(6):1373-1382. doi: 10.1007/s12265-023-10420-7. Epub 2023 Aug 16.
Penehyclidine hydrochloride (PHC) is an anticholinergic drug with cardioprotective effects. Ferroptosis is closely related to myocardial ischaemia-reperfusion injury (MIRI). In the present study, MIRI was induced in rats by left anterior descending coronary artery ligation. PHC pretreatment increased haemodynamic parameters and histopathological damage and reduced myocardial infarction size in the MIRI model. PHC pretreatment also inhibited ferroptosis, which was characterized by the decreased levels of Fe, 4-hydroxynonenal and ACSL4, and increased levels of GPX4, GSH-Px and GST. In response to 6 h of oxygen-glucose deprivation and 18 h of reoxygenation, PHC pretreatment had the same effects on these factors in H9c2 cells and reduced lipid ROS levels. Furthermore, ACSL4 overexpression reversed the protective effects of PHC on H9c2 cells. These results indicated that PHC inhibited MIRI through ACSL4-mediated ferroptosis. This study demonstrated that PHC could inhibit ferroptosis in MIRI and the relationship among PHC, ACSL4, ferroptosis and MIRI. This study demonstrated the inhibitory effect of PHC on ferroptosis and showed that PHC affects MIRI through ACSL4-mediated ferroptosis in vivo and in vitro.
盐酸戊乙奎醚（PHC）是一种具有心脏保护作用的抗胆碱能药物。铁死亡与心肌缺血再灌注损伤（MIRI）密切相关。在本研究中，通过结扎左冠状动脉前降支在大鼠中诱导MIRI。PHC预处理增加了血流动力学参数并减轻了组织病理学损伤，缩小了MIRI模型中的心肌梗死面积。PHC预处理还抑制了铁死亡，其特征是铁、4-羟基壬烯醛和ACSL4水平降低，以及GPX4、GSH-Px和GST水平升高。在缺氧缺糖6小时和复氧18小时的条件下，PHC预处理对H9c2细胞中的这些因子具有相同的作用，并降低了脂质活性氧水平。此外，ACSL4过表达逆转了PHC对H9c2细胞的保护作用。这些结果表明，PHC通过ACSL4介导的铁死亡抑制MIRI。本研究证明了PHC可抑制MIRI中的铁死亡以及PHC、ACSL4、铁死亡和MIRI之间的关系。本研究证明了PHC对铁死亡的抑制作用，并表明PHC在体内和体外通过ACSL4介导的铁死亡影响MIRI。
