Ioroi Tadaaki, Akao Masaharu, Iguchi Moritake, Kato Masashi, Kimura Takeshi, Izumi Yasuhiko, Akaike Akinori, Kume Toshiaki
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
J Pharmacol Sci. 2014;126(3):274-80. doi: 10.1254/jphs.14139fp. Epub 2014 Nov 1.
We previously reported that serofendic acid, a lipophilic extract of fetal calf serum, protects against oxidative stress in primary culture of neonatal rat cardiomyocytes. However, the effect of serofendic acid on myocardial ischemia-reperfusion injury in vivo is yet to be determined. In the present study, we investigated the effect of intravenous administration of serofendic acid on ischemia-reperfusion injury induced by transient occlusion of the left coronary artery in rats. The rat heart was subjected to 25-min ischemia followed by 2-h reperfusion. Bolus intravenous administration of serofendic acid (1-10 mg/kg) given twice reduced the infarct volume in a dose-dependent manner. The protective effect of serofendic acid was abolished by pretreatment with 5-hydroxydecanoate, a blocker of mitochondrial ATP-sensitive potassium channels. For further testing of the protective effect of serofendic acid at the subcellular level, we monitored mitochondrial membrane potential (MMP) in individual cells using real-time two-photon imaging of Langendorff-perfused rat heart. A 25-min no-flow ischemia, followed by reperfusion caused progressive MMP loss. Serofendic acid significantly reduced the number of cells undergoing MMP loss. These results suggest that serofendic acid protected cardiac myocytes against myocardial ischemia-reperfusion injury by preserving the functional integrity of mitochondria.
我们之前报道过,血清芬地酸,一种胎牛血清的亲脂性提取物,可保护原代培养的新生大鼠心肌细胞免受氧化应激损伤。然而,血清芬地酸对体内心肌缺血再灌注损伤的影响尚待确定。在本研究中,我们调查了静脉注射血清芬地酸对大鼠左冠状动脉短暂闭塞诱导的缺血再灌注损伤的影响。大鼠心脏经历25分钟的缺血,随后再灌注2小时。两次静脉推注血清芬地酸(1 - 10毫克/千克)以剂量依赖的方式减少了梗死体积。血清芬地酸的保护作用被线粒体ATP敏感性钾通道阻滞剂5 - 羟基癸酸预处理所消除。为了在亚细胞水平进一步测试血清芬地酸的保护作用,我们使用Langendorff灌注大鼠心脏的实时双光子成像监测单个细胞中的线粒体膜电位(MMP)。25分钟的无血流缺血,随后再灌注导致MMP逐渐丧失。血清芬地酸显著减少了经历MMP丧失的细胞数量。这些结果表明,血清芬地酸通过保持线粒体的功能完整性来保护心肌细胞免受心肌缺血再灌注损伤。