Role of microtubules in ischemic preconditioning against myocardial infarction
Role of microtubules in ischemic preconditioning against myocardial infarction
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DOI：
10.1016/j.cardiores.2004.07.013
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发表时间：
2004-11-01
影响因子：
10.8
通讯作者：
Shimamoto, K
中科院分区：
文献类型：
--
作者：
Nakamura, Y;Miura, T;Shimamoto, K
目的：在离体灌流的兔心脏中研究了微管在缺血预适应（PC）中的作用。方法：采用全脑缺血30 min，再灌注2 h的方法诱导心肌梗死，梗死面积以左心室的百分比（%IS/LV）表示。使用单独的组的兔子，在PC之前和之后取心室活检，用于测定蛋白激酶C（PKC）易位和p38-丝裂原活化蛋白激酶（p38 MAP激酶）活化。去微管，我们使用了两种结构不同的代理商，秋水仙碱（50 μ M）和诺考达唑（1 μ M）。结果：PC与两个周期的5分钟缺血/5分钟再灌注显着减少梗死面积从60.1 +/- 5.0%至20.0 +/-5.0%。虽然秋水仙碱和诺考达唑都不能改变非预处理心脏的梗死面积，但这些药物可以消除PC的梗死面积限制作用（%IS/LV分别为56.1 +/- 6.0%和53.5 +/-2.5%）。秋水仙素可抑制PC引起的PKC-MAPK转位和p38 MAP激酶激活。在非缺血性心脏1-oleyl-2-acetyl-sn-glycerol的输注也阻止了PKC的易位，由秋水仙素。结论：微管作为一种支持活化的PKC易位的机制，在PC抗梗死耐受的发展中起着至关重要的作用。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: The role of microtubules in ischemic preconditioning (PC) was investigated in isolated perfused rabbit hearts.Methods: Myocardial infarction was induced by 30-min global ischemia and 2-h reperfusion, and infarct size was expressed as a percentage of the left ventricle (%IS/LV). Using separate groups of rabbits, ventricular biopsies were taken before and after PC for determination of protein kinase C (PKC) translocation and p38-mitogen-activated protein kinase (p38MAP kinase) activation. To depolymerize microtubules, we used two structurally different agents, colchicine (50 muM) and nocodazole (1 muM).Results: PC with two cycles of 5-min ischemia/5-min reperfusion significantly reduced infarct size from 60.1 +/- 5.0% to 20.0 +/- 5.0%. Although neither colchicine nor nocodazole modified infarct size in nonpreconditioned hearts, these agents abolished the infarct size-limiting effects of PC (%IS/LV=56.1 +/- 6.0% and 53.5 +/- 2.5%, respectively). Colchicine prevented translocation of PKC-epsilon and p38MAP kinase activation by PC. PKC translocation by infusion of 1-oleyl-2-acetyl-sn-glycerol in nonischemic hearts was also prevented by colchicine.Conclusion: Microtubules play a crucial role in the development of anti-infarct tolerance by PC as a mechanism supporting translocation of activated PKC. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.