Contribution of mitochondrial K_<ATP> channel to cardioprotection against hypoxia or ischemia in rat cultured myocytes and isolated blood-perfused hearts

线粒体 K_<ATP> 通道对大鼠培养肌细胞和离体血液灌注心脏缺氧或缺血的心脏保护作用的贡献

• 批准号: 13670756
• 负责人: ASAYAMA Jun
• 金额: $ 1.79万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670756/
• 关键词: Cultured myocyte; mitochondrial K_<ATP> channel; reperfusion injury; reoxygenation injury; myocardial stretch; ACE-inhibitor; 心筋アポトーシス; IL-1β; ACE-I

1. The present study was designed to examine whether an angiotensin-converting enzyme inhibitor, temocapril, directly protects cardiac myocytes against hypoxia/reoxygenation injury via sarcolemmal K_<ATP> channel and/or mitochondrial K_<ATP> channel. Neonatal rat cardiac myocytes in primary culture were exposed to hypoxia for 5 hours and subsequently reoxygenated for 2 hours. Myocytes injury was estimated by the release of lactate dehydrogenase (LD). Temocapril significantly inhibited LD release after hypoxia/re-oxygenation in a dose-dependent manner. Pinacidil and diazoxide decreased LD release slightly. Glibenclamide, and 5-hydroxy-decanoic acid did not attenuate a cardioprotective effect of temocapril on LD release from cultured myocytes. Our results demonstrate that an angiotensin-converting enzyme inhibitor does not target K_<ATP> channel on the mechanism of carioprotection against hypoxia/reoxygenation injury. 2. The aim of the study was to determine whether myocardial stretch, w … More hich was proposed to activate K_<ATP>, caused by an increase in left ventricular end-diastolic pressure (LVEDP) could precondition post-ischemic myocardium. The blood-perfused hearts were subjected to 20 min of global no-flow ischemia followed by 30 min of reperfusion. In control group, LVEDP was set at 10 mmHg. In stretch group, LVEDP was increased to 30 or 60 mmHg for 5 min before global ischemia. The buffer-perfused hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. In stretch group, LVEDP was increased to 30 or 60 mmHg for 5 min or 15 min before global ischemia. Hemodynamic parameters at 30 min of reperfusion improved in both 30 mmHg- and 60 mmHg-stretch groups of blood-perfused hearts, and in 30 mmHg-stretch group of buffer-perfused hearts in stretch-duration time dependent way. Myocardial stretch induced by increasing LVEDP preconditioned both blood-perfused and buffer-perfused rat hearts, via mechanisms not involving myocardial ischemia during stretch. Less

1.本研究旨在探讨血管紧张素转换酶抑制剂替莫普利是否通过心肌细胞膜钾通道和/或线粒体钾通道直接保护心肌细胞免受缺氧/复氧损伤<ATP><ATP>。将原代培养的新生大鼠心肌细胞暴露于缺氧5小时，随后再氧合2小时。以乳酸脱氢酶（LD）的释放来评价心肌细胞的损伤。Temocapril以剂量依赖性方式显著抑制缺氧/复氧后LD的释放。吡那地尔和二氮嗪轻微减少LD释放。格列本脲和5-羟基癸酸没有减弱替莫普利对培养的心肌细胞释放LD的心脏保护作用。本研究结果表明，血管紧张素转换酶抑制剂<ATP>对缺氧/复氧损伤的心肌保护作用机制并非以钾通道为靶点。2.这项研究的目的是确定心肌牵张， ...更多信息 提示其激活K_2<ATP>，使左室舒张末压（LVEDP）升高，可预处理缺血后心肌。血液灌注的心脏进行20分钟的全脑无血流缺血，然后再灌注30分钟。对照组将LVEDP设定为10 mmHg。牵张组于缺血前5 min将LVEDP升至30或60 mmHg。将缓冲液灌注的心脏进行30分钟的全脑缺血，然后再灌注30分钟。牵张组于缺血前5 min或15 min将LVEDP升至30或60 mmHg。再灌注30 min时，血液灌流心脏30 mmHg和60 mmHg牵张组的血流动力学参数均得到改善，缓冲液灌流心脏30 mmHg牵张组的血流动力学参数也得到改善，且呈牵张持续时间依赖性。通过增加LVEDP预处理血液灌注和缓冲液灌注的大鼠心脏诱导心肌牵张，通过不涉及牵张过程中心肌缺血的机制。少

项目成果

Shiraishi Jun: "Important role of enrergy-dependent mitochondrial pathways in cultured ratcardiac myocyte apoptosis"Am J Physiol Heart Circ Physiol.. 281. H1637-H1647 (2001)

白石淳：“能量依赖性线粒体途径在培养的大鼠心肌细胞凋亡中的重要作用”Am J Physiol Heart Circ Physiol.. 281. H1637-H1647 (2001)