Nagai S, Miyazaki Y, Ogawa K, Satake T, Sugiyama S, Ozawa T
J Mol Cell Cardiol. 1985 Sep;17(9):873-84. doi: 10.1016/s0022-2828(85)80101-2.
The mechanism of mitochondrial damage during reperfusion injury of ischemic myocardium was studied using mongrel dogs in vivo and isolated mitochondria in vitro. Seventy-seven adult dogs were divided into three groups: the control group (n = 38), the Coenzyme Q10 (CoQ10)-5 mg group (n = 24), and the CoQ10-15 mg group (n = 15). In the control group, the left anterior descending coronary artery (LAD) of the dog was occluded for 15 min followed by 5 min of reperfusion after 40 min of premedication with physiological saline. In both CoQ10 groups, 5 mg/kg or 15 mg/kg of CoQ10 was infused intravenously for 20 min and then physiological saline was administered for 20 min before 15 min occlusion of the LAD. Subsequently, reperfusion was allowed for 5 min. Each group was further divided into two subgroups depending on the presence (arrhythmia group) or the absence (non-arrhythmia group) of ventricular arrhythmias. Immediately after 15 min occlusion, myocardial samples were taken from the normal and reperfused areas to measure CoQ10 content of myocardium. Heart mitochondria were prepared after 5 min of reperfusion from both areas. Arrhythmias appeared in 12 of 38 dogs in the control group (32%), two of 24 dogs in the CoQ10-5 mg group (8%) and none of 15 dogs in the CoQ10-15 mg group (0%). Premedication with CoQ10 increased tissue CoQ10 content in a dose-dependent manner. In the CoQ10-5 mg group, the increase in CoQ10 content of dogs with reperfusion arrhythmias was relatively less than that of dogs without reperfusion arrhythmias. In each group, mitochondrial function was decreased in the arrhythmia group compared to that of the non-arrhythmia group. The increase in free fatty acid (FFA) content and the decrease in phospholipid content were also observed in mitochondria from the reperfused area of each arrhythmia group. The increase in FFA and mitochondrial dysfunction were induced by the incubation of mitochondria in vitro with phospholipase (PLase) A2 or PLase C, and protected by the addition of CoQ10. These results suggest that PLase plays an important role in the development of mitochondrial damage associated with reperfusion.
采用杂种犬在体实验和体外分离线粒体的方法，研究缺血心肌再灌注损伤期间线粒体损伤的机制。77只成年犬分为三组：对照组（n = 38）、辅酶Q10（CoQ10）-5mg组（n = 24）和CoQ10-15mg组（n = 15）。对照组中，犬左冠状动脉前降支（LAD）闭塞15分钟，在生理盐水预处理40分钟后再灌注5分钟。在两个CoQ10组中，静脉输注5mg/kg或15mg/kg的CoQ10 20分钟，然后在LAD闭塞15分钟前给予生理盐水20分钟。随后，进行5分钟的再灌注。根据是否存在室性心律失常，每组进一步分为两个亚组（心律失常组和非心律失常组）。在LAD闭塞15分钟后，立即从正常和再灌注区域采集心肌样本，测量心肌CoQ10含量。再灌注5分钟后，从两个区域制备心脏线粒体。对照组38只犬中有12只出现心律失常（32%），CoQ10-5mg组24只犬中有2只出现心律失常（8%），CoQ10-15mg组15只犬中无一出现心律失常（0%）。CoQ10预处理可使组织CoQ10含量呈剂量依赖性增加。在CoQ10-5mg组中，有再灌注心律失常的犬CoQ10含量的增加相对低于无再灌注心律失常的犬。在每组中，心律失常组的线粒体功能均低于非心律失常组。在每个心律失常组的再灌注区域的线粒体中，还观察到游离脂肪酸（FFA）含量增加和磷脂含量降低。体外将线粒体与磷脂酶（PLase）A2或PLase C孵育可诱导FFA增加和线粒体功能障碍，而添加CoQ10可起到保护作用。这些结果表明，PLase在与再灌注相关的线粒体损伤发展中起重要作用。
