Department of Toxicology, School of Preventive Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Food Chem Toxicol. 2011 Nov;49(11):2750-7. doi: 10.1016/j.fct.2011.07.065. Epub 2011 Aug 6.
Myocardial ischemia/reperfusion (MI/R) is a major cause for the events of cardiovascular disease. Oxidative stress plays a critical role in the development of ischemia/reperfusion (IR) injury. As a potent antioxidant, alpha-lipoic acid (LA) has been shown to provide a benefit for the inhibition of IR injury and inhibit reactive oxygen species (ROS) generation during MI/R in rats. However, the mechanism on the protective effect of LA is still to be clarified. The present study was aimed to investigate the protective effect of LA against MI/R injury and its mechanisms. We found that 2h of myocardial ischemia followed by different time periods of reperfusion resulted in significant increase of creatine kinase (CK) activity. MI/R also significantly promoted oxidative stress and decreased the activities of antioxidant enzymes. In addition, apoptosis and inflammatory response were activated and aggravated in a time-dependent manner by MI/R. All these alterations induced by MI/R were attenuated by the administration of LA 30 min before reperfusion. These results suggested that LA played a protective effect against MI/R injury via antioxidant, anti-apoptotic and anti-inflammatory effects. These findings may significantly better the understanding of the pharmacological actions of LA and advance therapeutic approaches to MI/R injury and cardiovascular diseases.
心肌缺血/再灌注（MI/R）是心血管疾病事件的主要原因。氧化应激在缺血/再灌注（IR）损伤的发展中起着关键作用。作为一种有效的抗氧化剂，硫辛酸（LA）已被证明可抑制 IR 损伤，并抑制大鼠 MI/R 期间活性氧（ROS）的产生。然而，LA 的保护作用机制仍有待阐明。本研究旨在探讨 LA 对 MI/R 损伤的保护作用及其机制。我们发现，心肌缺血 2 小时后再灌注不同时间会导致肌酸激酶（CK）活性显著增加。MI/R 还显著促进氧化应激，降低抗氧化酶的活性。此外，MI/R 以时间依赖性方式激活和加重细胞凋亡和炎症反应。MI/R 引起的所有这些改变在再灌注前 30 分钟给予 LA 后均减轻。这些结果表明，LA 通过抗氧化、抗凋亡和抗炎作用对 MI/R 损伤发挥保护作用。这些发现可能会更好地理解 LA 的药理学作用，并推进 MI/R 损伤和心血管疾病的治疗方法。
