dl-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress

作者：Zhou, Xiufang; Tang, Si; Hu, Ke^*; Zhang, Zhan; Liu, Pei; Luo, Yuchuan; Kang, Jing; Xu, Lifang

来源：Sleep and Breathing, 2018, 22(3): 853-863.

DOI：10.1007/s11325-018-1656-0

• Chronic intermittent hypoxia
• dl-Propargylglycine
• Myocardial injury
• Apoptosis
• Oxidative stress
• Endoplasmic reticulum stress

BackgroundChronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of dl-propargylglycine (PAG), an effective inhibitor of cystathionine -lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial.PurposeThe present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH.MethodsSprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected.ResultsIn NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group.ConclusionThese results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.

• 出版日期2018-9
• 单位武汉大学