Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China.
Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Minzu University, Enshi, Hubei Province, China.
Biomed Pharmacother. 2024 Nov;180:117560. doi: 10.1016/j.biopha.2024.117560. Epub 2024 Oct 22.
Acute myocardial ischemia/reperfusion injury (MIRI) with complicated mechanisms contributes to a high risk of ventricular arrhythmia, high lethality, and even sudden death. In vitro, Fraxinellone (FRA) exhibits an array of biologic activities and may possess cardioprotective effects. However, no relevant studies have examined FRA's protective potential against MIRI and related ventricular arrhythmias. The present study was undertaken to determine the effectiveness of FRA on MIRI and ventricular fibrillation (VF) susceptibility in rats and to elucidate the underlying mechanisms.
48 healthy male Sprague-Dawley (SD) rats were randomly divided into the following four groups: Sham+vehicle(n=12), Sham+FRA(n=12), I/R+vehicle(n=12) and I/R+FRA(n=12). Histopathology, electrophysiological examination, HRV analysis in combination with molecular biology were used to investigate the therapeutic benefits of FRA on cardiac injury and VF susceptibility during myocardial IR. Finally, the potential mechanism by which FRA protects myocardium from MIRI was explored.
Pretreatment with FRA ameliorated myocardial fibrosis after MIRI in vivo, alleviated myocardial injury, inflammation, oxidative stress and apoptosis in vivo and in vitro, thereby protecting myocardium from MIRI injury. In addition, FRA administration could improve HRV, prolong ventricular effective refractory period (ERP) and action potential duration (APD), attenuate VF induction rate, and contribute to improving ventricular sympathetic nerve remodeling and ion channel remodeling. Mechanistically, FRA may reduce MIRI via the PI3K/AKT pathway.
FRA may exert cardioprotective effects during MIRI by inhibiting myocardial inflammation, oxidative stress and apoptosis, and decrease VF susceptibility by improving sympathetic remodeling and ion channel remodeling, which might represent a potential therapeutic strategy for attenuation of MIRI.
急性心肌缺血/再灌注损伤（MIRI）机制复杂，易导致室性心律失常、高死亡率甚至猝死。体外研究表明，水飞蓟宾（FRA）具有多种生物学活性，可能具有心脏保护作用。但目前尚无研究探讨 FRA 对 MIRI 及相关室性心律失常的保护作用。本研究旨在探讨 FRA 对大鼠 MIRI 及室颤（VF）易感性的影响，并阐明其作用机制。
48 只健康雄性 Sprague-Dawley（SD）大鼠随机分为 4 组：假手术+载体组（n=12）、假手术+FRA 组（n=12）、缺血再灌注+载体组（n=12）和缺血再灌注+FRA 组（n=12）。采用组织病理学、电生理学检查、HRV 分析结合分子生物学方法，探讨 FRA 对心肌 IR 中心肌损伤和 VF 易感性的治疗作用。最后，探讨 FRA 保护心肌免受 MIRI 的潜在机制。
FRA 预处理可改善体内 MIRI 后的心肌纤维化，减轻心肌损伤、炎症、氧化应激和细胞凋亡，从而保护心肌免受 MIRI 损伤。此外，FRA 给药可改善 HRV，延长心室有效不应期（ERP）和动作电位时程（APD），降低 VF 诱导率，有助于改善心室交感神经重塑和离子通道重塑。机制上，FRA 可能通过 PI3K/AKT 通路减轻 MIRI。
FRA 可能通过抑制心肌炎症、氧化应激和细胞凋亡发挥 MIRI 保护作用，通过改善交感神经重塑和离子通道重塑降低 VF 易感性，可能为减轻 MIRI 提供一种潜在的治疗策略。
