Signal Transduction in the Cardioprotective Effect of Light Alcohol and its clinical application for ischemic preconditioning

淡醇心脏保护作用中的信号转导及其缺血预处理的临床应用

• 批准号: 12670706
• 负责人: MIYAMAE Masami
• 金额: $ 0.77万
• 依托单位: Osaka Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670706/
• 关键词: ischemia; reperfusion; alcohol; reactie oxygen species; phospholipase C; high enegy phosphate; preconditioning; guineapig

Epidemiologic studies have shown that light to moderate ethanol use is associated with a protective effect against fatal coronary artery disease. We showed that the cardioprotective effect of ethanol requires adenosine A1 receptor activation at the time of ischemia, like experimental ischemic preconditioning(PC). We investigated the potetial downstream mediators of this protection, compared with PC. Furthermore, PC preserves myocardial high-energy phosphate metabolites (HEP) and intracellular pH (pHi) during subsequent sustained ischemia. Reactive oxygen species (ROS) generation may be required to mediate PC, we examined the effects of inhibiting ROS generatio during a PC protocol in vivo using an open-chest porcine model.1. Is phospholipase C (PLC) involved in the cardioprotective effect of light ethanol?Hearts were isolated from guinea pigs after drinkng 2.5% ethanol for 16 weeks and were subjected to global ischemia and reperfusion using Langendorff apparatus. Hearts from animals dr … More inking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. PLC blockade with U-73122 abolished the protection provided by ethanol consumption. These findings indicate that long-term light alcohol consumption reduces myocardial ischemia-reperfusion injury and that PLC is required for this cardioprotective effect of ethanol. This cardioprotective effect of long-term light alcohol consumption mimics PC and may, in part, account for the beneficial effect of light drinking on cardiac health2. Is PC mediated by reactive oxygen species produced during PC protocol?PC preserves myocardial HEP and intracellular pHi during subsequent sustained ischemia. 31P-NMR data was correlated with myocyte ultrastructural changes using electron microscopy. Open chest pigs underwent 60 minutes of left anterior descending coronary artery occlusion. PC was elicited by a single episode of 5-minute occlusion and 5-minute reperfusion. The cell diffusible free radical scavenger, N-2- mercaptopropionyl glycine (MPG) or placebo saline were infused for 40 minutes starting 30 minutes before PC (PC+MPG group ＆ PC group). Following PC, ATP and pHi were significantly preserved through 25 min of ischemia and phosphocreatine through 20 min of ischemia. This preservation of HEP and pHi was abolished by inhibiting ROS generation with MPG. HEP preservation with PC was associated with reduced ultrastructural damage as demonstrated by electron microscopy, including less myocyte swelling, myofibrillar disruption and nuclear chromatin marginationThese results suggest that the cardioprotective effect of light alcohol can be used for clinical application as a chronic ischemic preconditioning Less

流行病学研究表明，光到中度乙醇的使用与针对致命冠状动脉疾病的保护作用有关。我们表明，乙醇的心脏保护作用需要在缺血时腺苷A1受体激活，例如实验性缺血性预处理（PC）。与PC相比，我们研究了该保护的潜在下游介质。此外，在随后持续性缺血期间，PC保留了心肌高能代谢产物（HEP）和细胞内pH（PHI）。可能需要用反应性氧（ROS）产生介导PC，我们检查了使用开放式猪猪型在体内抑制ROS Exenation的效果。1。磷脂酶C（PLC）是否参与光乙醇的心脏保护作用？心脏在饮用2.5％乙醇后从豚鼠中分离出16周，并使用Langendorff Appatus进行全球性缺血和再灌注。与对照组相比，动物的心脏……更多的墨水乙醇表现出改善的功能恢复和改善的肌细胞损伤。与U-73122的PLC封锁废除了乙醇消耗提供的保护。这些发现表明，长期的轻饮用饮用量可减少心肌缺血 - 灌注损伤，并且需要PLC才能对乙醇的这种心脏保护作用。长期轻饮用饮酒的这种心脏保护作用模仿了PC，可能部分原因是轻饮用对心脏健康的有益作用2。 PC是否是由PC方案过程中产生的活性氧介导的？PC可以保留在随后的持续缺血期间的心肌HEP和细胞内PHI。 31P-NMR数据与使用电子显微镜的心肌细胞超微结构变化相关。开放的胸猪接受了60分钟的左前冠状动脉阻塞。 PC是由5分钟的闭塞和5分钟再灌注的单个发作引起的。在PC（PC+MPG组和PC组）之前，将细胞扩散自由基清除剂，N-2-膀胱甘氨酸（MPG）或安慰剂盐水注入40分钟。在PC之后，直到缺血20分钟，ATP和PHI得到了显着保存到25分钟的缺血和磷酸盐。通过用MPG抑制ROS产生的HEP和PHI的保存被废除。通过电子显微镜证明，使用PC的HEP保存与降低的超微结构损伤有关，包括较少的肌细胞肿胀，肌原纤维破坏和核染色质细分，从而表明，轻度酒精的心脏保护作用可用于临床应用，以减少慢性缺血性预测。