Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction.
Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction.
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DOI：
10.1007/s10557-010-6222-3
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发表时间：
2010-02
影响因子：
3.4
通讯作者：
Mocanu, Mihaela M.
中科院分区：
文献类型：
--
作者：
Paiva, Marta A.;Goncalves, Lino M.;Providencia, Luis A.;Davidson, Sean M.;Yellon, Derek M.;Mocanu, Mihaela M.
AMPK在心脏能量代谢的调节中起着至关重要的作用。在缺血期间，AMPK激活是一种已知的适应性促生存机制，有助于维持心肌的能量水平。然而，仍然不清楚在再灌注期间AMPK的激活是否对心脏有益。两种已知的AMPK激活剂（二甲双胍和AICAR）用于验证再灌注时AMPK的短暂激活可发挥心脏保护作用的假设，如心肌梗死面积的减小所反映的。灌注的大鼠心脏进行35分钟缺血和120分钟再灌注。在再灌注开始时，单独或与AMPK抑制剂化合物C（CC，10 μM）一起加入二甲双胍（50 μM）或AICAR（0.5 mM）15 min。测量细胞大小和α-AMPK磷酸化。二甲双胍显著降低了梗死面积，从对照组的47.8±1.7%降至31.4± 2.9%，当同时给予药物时，CC消除了这种作用。类似地，AICAR也诱导梗死面积显著减少至32.3± 4.8%，CC也消除了该作用。然而，二甲双胍的保护并没有取消，如果CC是在再灌注后期管理。此外，在再灌注的最初30分钟期间，二甲双胍治疗组中α-AMPK磷酸化显著增加。我们的数据表明，在我们的离体心肌缺血再灌注损伤模型中，AMPK在早期再灌注中的激活与梗死面积的减少有关。
AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size. Perfused rat hearts were subjected to 35 min ischaemia and 120 min reperfusion. Metformin (50 μM) or AICAR (0.5 mM) were added for 15 min at the onset of reperfusion alone or with Compound C (CC, 10 μM), an AMPK inhibitor. Infarct size and α-AMPK phosphorylation were measured. Metformin significantly reduced infarct size from 47.8±1.7% in control to 31.4±2.9%, an effect abolished by CC when the drugs were given concomitantly. Similarly, AICAR also induced a significant reduction in infarct size to 32.3±4.8%, an effect also abrogated by CC. However, metformin's protection was not abolished if CC was administered later in reperfusion. In addition, α-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion. Our data demonstrated that, in our ex vivo model of myocardial ischaemia-reperfusion injury, AMPK activation in early reperfusion is associated with a reduction in infarct size.
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DOI：
10.1111/j.1742-7843.2008.00234.x
发表时间：
2008-07-01
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
2004-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
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作者：
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DOI：
10.1152/ajpheart.00873.2007
发表时间：
2008-06-01
影响因子：
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作者：
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