Activation of Adenosine-Monophosphate-Activated Protein Kinase Abolishes Desflurane-Induced Preconditioning Against Myocardial Infarction In Vivo
Activation of Adenosine-Monophosphate-Activated Protein Kinase Abolishes Desflurane-Induced Preconditioning Against Myocardial Infarction In Vivo
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DOI：
10.1053/j.jvca.2010.02.007
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发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Lange, Markus
中科院分区：
文献类型：
--
作者：
Lotz, Christopher;Fisslthaler, Beate;Lange, Markus
目的：心肌缺血伴随着一磷酸腺苷活化蛋白激酶(AMPK)的快速激活。然而，目前尚不清楚这是否代表了缺血性损伤过程中的潜在有益或有害事件。AMPK激活在地氟烷诱导的预适应的心脏保护环境中的作用迄今尚未被研究。因此，本研究旨在探讨AMPK激活在地氟醚诱导的在体预适应中的作用。设计：前瞻性随机载体对照研究。地点：大学研究实验室。对象：雄性新西兰大白兔(n=44)。干预：冠状动脉阻断30分钟后再灌注3小时。CAO前30分钟给予地氟醚(最低肺泡浓度为1.0)，然后停用。不同组的动物接受AMPK激动剂5-氨基咪唑-4-甲酰胺-1-核糖苷(AICAR)单独或与地氟烷联合使用。心肌梗死面积采用重力法测定，AMPK活性和心肌糖原含量采用特异性分析方法测定。免疫印迹法检测AMPK底物乙酰辅酶A羧基酶的磷酸化。结果：地氟醚组心肌梗死面积(36.7±-1.9%)较对照组(61.6%+/-3.0%)显著缩小(P<0.05)，同时心肌组织糖原水平升高(2.09±0.07mU/g，P<；0.05)。AICAR单独激活AMPK对心肌缺血损伤(65%+/-3.3)无保护作用，但在增加心肌糖原消耗(1.42+/-0.15µg/mL)的同时，取消了地氟烷(61.8%+/-4.2%)对心肌的保护作用。结论：AMPK的药理激活可阻断地氟烷的心肌保护作用。(C)2011 Elsevier Inc.保留所有权利。
Objectives: Myocardial ischemia is accompanied by a rapid activation of adenosine-monophosphate-activated protein kinase (AMPK). However, it is unclear whether this represents a potentially beneficial or detrimental event in the course of ischemic injury. The role of AMPK activation in the cardioprotective setting of desflurane-induced preconditioning has not been investigated to date. Hence, the current study was undertaken to address the role of AMPK activation during desflurane-induced preconditioning in vivo.Design: A prospective randomized vehicle-controlled study.Setting: A university research laboratory.Subjects: Male New Zealand white rabbits (n = 44).Interventions: The animals were subjected to a 30-minute coronary artery occlusion (CAO) followed by 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and discontinued 30 minutes prior to CAO. Different groups of animals received the AMPK activator, 5-aminoimidazole-4-carboxamide-1-briboside (AICAR), alone or in combination with desflurane. Infarct size was determined gravimetrically; AMPK activity and myocardial glycogen content were measured using specific assays. Phosphorylation of the AMPK substrate, acetylCoA carboxylase, was assessed by immunoblotting. Data are mean +/- standard error of the mean.Results: Desflurane significantly reduced the myocardial infarct size (36.7 +/- 1.9%, p < 0.05) compared with the control group (61.6% +/- 3.0%), concomitant with increased myocardial tissue levels of glycogen (2.09 +/- 0.07 mu g, p < 0.05). Activation of the AMPK by AICAR alone did not protect against ischemic injury (65% +/- 3.3), but did abolish the cardioprotection elicited by desflurane (61.8% +/- 4.2%) at the same time as increasing myocardial glycogen consumption (1.42 +/- 0.15 mu g/mL).Conclusions: The results obtained show that the pharmacologic activation of AMPK abolishes cardioprotection elicited by desflurane. (C) 2011 Elsevier Inc. All rights reserved.