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Accumulation of non-esterified fatty acids in the myocardium during ischemia and substances that inhibit the accumulation of fatty acids

缺血时心肌内非酯化脂肪酸的积累以及抑制脂肪酸积累的物质

基本信息

批准号：
60480124
负责人：
ABIKO Yasushi
金额：
$ 3.78万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480124/
关键词：
ISCEMIC MYOCARDIUM NON-ESTERIFIED FATTY ACIDS PROPRANOLOL DOG 冠動脈

项目摘要

Occlusion of the coronary artery produces ischemia of the myocardium, resulting in physiological, biochemical, and hitological alterations of the myocardium. Coronary occlusion also produces acidosis of the myocardium, the exact mechanism for myocardial acidosis remaining unclear, however. One possibility is that ischemia increases breakdown of triglyceride and phospholipids in the myocardium, and releases protons. If this view is correct, the levels of non-esterified fatty acids in the myocardium would increase during ischemia, and a drug that inhibits ischemia-induced myocardial acidosis would attenuate accmulation of non-esterified fatty acids in the myocardium.In the present study, in the first place, we tried to find a method suitable for detection of non-esterified fatty acids in the myocardium, and found that the method develped by Nimura and Kinoshita using 9-anthryldiazomethane (ADAM) reagent for fluorescent labeling of carboxylic acids was most simple and reliable as well. Th … More e results show that the levels of lauric acid, myristic acid, palmitoleic acid, arachidonic acid, linoleic acid, palmitic acid, oleic acid, and stearic acid in the myocardium were 10.23, 48.29, 7.53, 25.48, 106.61, 135.02, 78.58, and 57.47 nmol/g wet tissue, respectively. Coronary artery occlusion for 90 min increased the levels of these non-esterified fatty acids to 1.70 - 3.38 times, the increase in arachidonic acid being most prominent. This result indicates that there is breakdown of triglyceride and/or phospholipids. An injection of propranolol (1 mg/kg) given intravenously 5 min before coronary occlusion inhibited completely the ischemia-induced increase in non-esterified fatty acids. A dextro-isomer of propranolol (1 mg/kg) also tended to attenuate the increase in non-esterified fatty acids.These results suggest that coronary artery occlusion produces release of catecholaimnes in the myocardium, and the released catecholamines activate lipases and phospholipases to release non-esterified fatty acids. The membrane stabilizing action of propranolol may also contribute to the inhibitory action of propranolol on the ischemia-induced increase in fatty acids. Less

冠状动脉闭塞引起心肌缺血，引起心肌的生理、生化和组织学改变。冠状动脉闭塞也可引起心肌酸中毒，但心肌酸中毒的确切机制尚不清楚。一种可能是缺血增加心肌中甘油三酯和磷脂的分解，并释放质子。如果这种观点是正确的，心肌中的非酯化脂肪酸水平将在缺血期间增加，抑制缺血引起的心肌酸中毒的药物将减轻心肌中非酯化脂肪酸的积累。在本研究中，我们首先试图寻找一种适合检测心肌中非酯化脂肪酸的方法，发现Nimura和Kinoshita开发的使用9-蒽基二氮甲烷（ADAM）试剂荧光标记羧酸的方法也是最简单可靠的。结果表明：心肌湿组织中月桂酸、肉豆蔻酸、棕榈油酸、花生四烯酸、亚油酸、棕榈酸、油酸、硬脂酸含量分别为10.23、48.29、7.53、25.48、106.61、135.02、78.58、57.47 nmol/g。冠状动脉闭塞90分钟后，这些非酯化脂肪酸的水平增加了1.70 - 3.38倍，其中花生四烯酸的增加最为显著。这个结果表明有甘油三酯和/或磷脂的分解。冠状动脉闭塞前5分钟静脉注射心得安（1mg /kg）完全抑制缺血引起的非酯化脂肪酸的增加。心得安的右旋异构体（1mg /kg）也倾向于减弱非酯化脂肪酸的增加。这些结果表明，冠状动脉闭塞使心肌释放儿茶酚胺，释放的儿茶酚胺激活脂肪酶和磷脂酶释放非酯化脂肪酸。心得安的膜稳定作用也可能有助于心得安抑制缺血引起的脂肪酸增加。少