Wang Xiao, Song Shao-Ming, Lu Wen-Qiang, Zhao Yan, Lv Ren-Jun, He Yao, Dong Na, Yu Qin, Yue Hong-Mei
The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China.
Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
Eur J Pharmacol. 2025 May 5;994:177380. doi: 10.1016/j.ejphar.2025.177380. Epub 2025 Feb 13.
Obstructive sleep apnea syndrome (OSAS) is a prevalent sleep-related breathing disorder characterized by intermittent hypoxia (IH). Myocardial injury is a common complication associated with OSAS. Alpha-lipoic acid (LA), a potent antioxidant, has been utilized in various disease contexts and has demonstrated significant protective effects in myocardial infarction models. Given the limited treatment options available for OSAS-related myocardial injury, this study aimed to demonstrate the potential therapeutic effects of LA and to investigate the underlying mechanisms. IH is a widely employed method to simulate the pathophysiological conditions associated with OSAS. In vivo experiments were conducted using mice placed in a specialized hypoxic chamber to replicate IH conditions. Echocardiography indicated that exposure to IH severely impaired cardiac function. Treatment with LA activated the Nrf2 pathway and autophagy, which contributed to the improvement of cardiac function in mice with OSAS. Additionally, in vitro studies demonstrated that IH induced apoptosis and decreased cell viability in H9C2 cardiomyocytes. LA enhanced Nrf2 nuclear translocation and its downstream signaling pathways, thereby promoting autophagy, inhibiting apoptosis, and alleviating injury in H9C2 cardiomyocytes. Furthermore, in vitro inhibition of Nrf2 using ML385 reduced autophagy levels and attenuated the protective effects of LA against apoptosis in H9C2 cardiomyocytes. These findings suggest that LA may provide a promising therapeutic strategy for myocardial injury associated with OSAS. By elucidating these findings, new insights into the protective mechanisms of LA against IH-induced myocardial injury are provided, highlighting its potential as a therapeutic agent for diseases associated with OSAS.
阻塞性睡眠呼吸暂停综合征（OSAS）是一种常见的与睡眠相关的呼吸障碍，其特征为间歇性缺氧（IH）。心肌损伤是与OSAS相关的常见并发症。α-硫辛酸（LA）是一种强效抗氧化剂，已被应用于各种疾病背景，并在心肌梗死模型中显示出显著的保护作用。鉴于OSAS相关心肌损伤的治疗选择有限，本研究旨在证明LA的潜在治疗作用并探究其潜在机制。IH是一种广泛用于模拟与OSAS相关的病理生理状况的方法。体内实验使用置于专门缺氧舱中的小鼠进行，以复制IH状况。超声心动图表明，暴露于IH会严重损害心脏功能。LA治疗激活了Nrf2通路和自噬，这有助于改善OSAS小鼠的心脏功能。此外，体外研究表明，IH诱导H9C2心肌细胞凋亡并降低细胞活力。LA增强了Nrf2核转位及其下游信号通路，从而促进自噬、抑制凋亡并减轻H9C2心肌细胞的损伤。此外，使用ML385体外抑制Nrf2可降低自噬水平，并减弱LA对H9C2心肌细胞凋亡的保护作用。这些发现表明，LA可能为与OSAS相关的心肌损伤提供一种有前景的治疗策略。通过阐明这些发现，为LA对IH诱导的心肌损伤的保护机制提供了新的见解，突出了其作为与OSAS相关疾病治疗剂的潜力。
