Alpha-lipoic acid alleviated intermittent hypoxia-induced myocardial injury in mice by promoting autophagy through Nrf2 signaling pathway

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.