Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase
Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase
复制标题
DOI：
10.1016/j.regpep.2007.10.002
复制
发表时间：
2008-02-07
影响因子：
--
通讯作者：
Baxter, Gary F.
中科院分区：
文献类型：
--
作者：
Kleinz, Matthias J.;Baxter, Gary F.
Apelin是G蛋白偶联APJ受体的内源性配体，是一种在心脏中具有新兴调节作用的肽介质：本研究的目的是探索Apelin/APJ系统在心肌缺血/再灌注损伤中的潜在作用。为了确定心脏Apelin/APJ的表达和急性缺血损伤的潜在调节，Langendorff灌注的大鼠心脏经受局部缺血（左冠状动脉闭塞，35 min）或缺血，随后再灌注（30 min），然后通过rt-PCR测定心室肌中Apelin和APJ mRNA的表达。与APJ mRNA表达保持不变不同，apelin mRNA在单独缺血的离体大鼠心脏的心室肌中上调2.4倍，但在再灌注30分钟后恢复到对照水平。然后，我们继续测试用外源性爱帕琳肽治疗对缺血/再灌注损伤具有保护作用的假设。灌流心脏进行左冠状动脉主干闭塞35分钟和120分钟的再灌注，之后通过四唑染色确定梗死面积。从冠状动脉闭塞前5分钟至再灌注后15分钟或从再灌注前5分钟至再灌注后15分钟灌注外源性Pyr（I）-爱帕琳-13（10（-8）M）。虽然在缺血期间单独使用时无效，但在再灌注期间施用的爱帕琳显著降低了经受暂时冠状动脉闭塞随后再灌注的心脏中的梗死面积（缺血风险区的47.6 +/-2.6%相比于对照中的62.6 +/-2.8%，各n=10，p < 0.05）。这种保护作用没有被PI 3 K抑制剂渥曼青霉素（10（-7）M，梗死面积49.8 +/-4.1%，n=4）或P70 S6激酶抑制剂雷帕霉素（10（-9）M，41.8 +/-8.8%，n=4）的联合给药所消除。总之，这些结果表明，爱帕琳可能是一个新的和潜在的重要的心脏保护autacoid，心肌缺血后迅速上调，并通过一个未知的途径。(C)2007 Elsevier B. V.保留所有权利。
Apelin, the endogenous ligand of the G protein-coupled APJ receptor, is a peptide mediator with emerging regulatory actions in the heart: The aim of the present studies was to explore potential roles of the apelin/APJ system in myocardial ischaemia/reperfusion injury. To determine the cardiac expression of apelin/APJ and potential regulation by acute ischaemic insult, Langendorff perfused rat hearts were subjected to regional ischaemia (left coronary artery occlusion, 35 min) or ischaemia, followed by reperfusion (30 min), Apelin and APJ mRNA expression were then determined in ventricular myocardium by rt-PCR. Unlike APJ mRNA expression, which remained unchanged, apelin mRNA was upregulated 2.4 fold in ventricular myocardium from isolated rat hearts undergoing ischaemia alone, but returned back to control levels after 30 min reperfusion. We then proceeded to test the hypothesis that treatment with exogenous apelin is protective against ischaemia/reperfusion injury. Perfused hearts were subjected to 35 min left main coronary artery occlusion and 120 min reperfusion, after which infarct size was determined by tetrazolium staining. Exogenous Pyr(I)-apelin-13 (10(-8) M) was perfused either from 5 min prior to 15 min after coronary occlusion, or from min prior to 15 min after reperfusion. Whilst ineffective when used during ischaemia alone, apelin administered during reperfusion significantly reduced infarct size (47.6 +/- 2.6% of ischaemic risk zone compared to 62.6 +/- 2.8% in control, n=10 each, p < 0.05) in hearts subject to temporary coronary occlusion followed by reperfusion. This protective effect was not abolished by co-administration of the PI3K inhibitor wortmannin (10(-7) M, infarct size 49.8 +/- 4.1%, n=4) or the P70S6 kinase inhibitor rapamycin (10(-9) M, 41.8 +/- 8.8%, n=4). In conclusion these results suggest that apelin may be a new and potentially important cardioprotective autacoid, upregulated rapidly after myocardial ischaemia, and acting through an unknown pathway. (C) 2007 Elsevier B.V. All rights reserved.