Department of Anesthesiology, Oita University Faculty of Medicine, Oita, Japan.
Crit Care Med. 2011 Mar;39(3):506-11. doi: 10.1097/CCM.0b013e318206b7e7.
Myocardial ischemia/reperfusion injury is a life-limiting condition. Reactive oxygen species are released upon reperfusion, resulting in damage to myocardial cells. Accordingly, antioxidant drugs have been shown to protect the myocardium against ischemia/reperfusion injury. The purpose of the present study was to determine the cardioprotective effects of the new lipoic acid-derivative drug sodium zinc dihydrolipoylhistidinate in a global ischemia isolated perfused rat heart model.
Animals were randomly divided into five groups: 1) normal group, 2) control ischemia/reperfusion group, 3) high-dose sodium zinc dihydrolipoylhistidinate (1 ng/mL) plus ischemia/reperfusion group, 4) medium-dose sodium zinc dihydrolipoylhistidinate (0.1 ng/mL) plus ischemia/reperfusion group, or 5) low-dose sodium zinc dihydrolipoylhistidinate (0.01 ng/mL) plus ischemia/reperfusion group.
University medical center research laboratory.
Male Sprague-Dawley rats weighing 250-300 g.
Hearts underwent ischemia/reperfusion after isolation with or without sodium zinc dihydrolipoylhistidinate treatment. We then conducted cardiac histopathology and transmission electron microscopy analyses and assessed cardiac function. In addition, we examined the effects of sodium zinc dihydrolipoylhistidinate on ischemia/reperfusion-induced mitochondrial dysfunction. We found that cardiac dysfunction and mitochondrial damage were significantly reduced after reperfusion by sodium zinc dihydrolipoylhistidinate treatment. However, only rats treated with high-dose sodium zinc dihydrolipoylhistidinate showed improved cardiac function. Furthermore, treatment with sodium zinc dihydrolipoylhistidinate significantly improved mitochondrial function in vitro.
These findings suggest that sodium zinc dihydrolipoylhistidinate attenuates ischemia/reperfusion-induced myocardial dysfunction in rats. Furthermore, sodium zinc dihydrolipoylhistidinate exerted cardioprotective effects via preservation of mitochondrial function. Taken together, our results strongly support the potential therapeutic role of sodium zinc dihydrolipoylhistidinate in the treatment of ischemia/reperfusion injury.
心肌缺血/再灌注损伤是一种危及生命的疾病。再灌注时会释放活性氧，导致心肌细胞损伤。因此，抗氧化药物已被证明可保护心肌免受缺血/再灌注损伤。本研究旨在确定新型硫辛酸衍生物药物二氢硫辛酸锌钠组氨酸在整体缺血分离灌流大鼠心脏模型中的心脏保护作用。
动物随机分为五组：1）正常组，2）对照缺血/再灌注组，3）高剂量二氢硫辛酸锌钠（1ng/ml）加缺血/再灌注组，4）中剂量二氢硫辛酸锌钠（0.1ng/ml）加缺血/再灌注组，或 5）低剂量二氢硫辛酸锌钠（0.01ng/ml）加缺血/再灌注组。
大学医学中心研究实验室。
雄性 Sprague-Dawley 大鼠，体重 250-300g。
心脏在分离后进行缺血/再灌注，或不进行二氢硫辛酸锌钠处理。然后进行心脏组织病理学和透射电镜分析，并评估心脏功能。此外，我们研究了二氢硫辛酸锌钠对缺血/再灌注诱导的线粒体功能障碍的影响。我们发现，再灌注后，二氢硫辛酸锌钠处理可显著减轻心脏功能障碍和线粒体损伤。然而，只有高剂量二氢硫辛酸锌钠处理的大鼠显示出改善的心脏功能。此外，二氢硫辛酸锌钠处理可显著改善体外线粒体功能。
这些发现表明，二氢硫辛酸锌钠可减轻大鼠缺血/再灌注引起的心肌功能障碍。此外，二氢硫辛酸锌钠通过保护线粒体功能发挥心脏保护作用。总之，我们的研究结果强烈支持二氢硫辛酸锌钠在治疗缺血/再灌注损伤中的潜在治疗作用。
