Brief left ventricular pressure overload reduces myocardial apoptosis
Brief left ventricular pressure overload reduces myocardial apoptosis
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DOI：
10.1016/j.jss.2014.10.042
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发表时间：
2015-03-01
影响因子：
2.2
通讯作者：
Huang, Cheng-Hsiung
中科院分区：
文献类型：
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作者：
Huang, Hsien-Hao;Lai, Chang-Chi;Huang, Cheng-Hsiung
背景：心肌缺血再灌注后细胞死亡与细胞凋亡和坏死有关。我们以前报道过，短暂的左心室压力超负荷(LVPO)可以减少心肌梗死(MI)的范围。在本研究中，我们探讨了短暂压力超负荷是否能减少细胞凋亡及其机制。材料和方法：结扎左冠状动脉前降支40分钟，再灌流3小时，建立雄性麻醉SD大鼠心肌梗死模型。短暂的LVPO是通过两次10分钟的升主动脉部分夹闭，使左心室收缩压高于基线的50%来实现的。缺血预适应由两次冠状动脉闭塞10分钟和再灌流10分钟引起。结果：短暂的左心室反搏和缺血预适应可显著降低心肌梗死面积(P<；0.001)。短暂的压力超负荷显著减少心肌细胞凋亡，表现为末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性核减少(P<；0.001)，很少或没有DNA梯状条带，caspase-3活性降低(P<；0.01)。此外，短暂的压力超负荷显著增加Bcl2(P<；0.001)，降低Bax(P<；0.001)和P53(P<；0.001)。短暂压力超负荷使AKT磷酸化显著增加(P<；0.001)，而c-jun氨基末端激酶磷酸化显著降低(P<；0.001)。血流动力学、危险面积和死亡率在不同组之间没有显著差异。结论：短暂左左室早搏可显著减少心肌细胞凋亡。其机制可能与调控Bcl2和Bax，抑制P53，增加Akt的磷酸化，抑制c-jun氨基末端激酶的磷酸化有关。(C)2015 Elsevier Inc.保留所有权利。
Background: Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved.Materials and methods: MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions.Results: Brief LVPO and ischemic preconditioning significantly decreased MI size (P < 0.001). Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P < 0.001), little or no DNA laddering, and reduced caspase-3 activation (P < 0.01). Moreover, brief pressure overload significantly increased Bcl-2 (P < 0.001) and decreased Bax (P < 0.001) and p53 (P < 0.01). Akt phosphorylation was significantly increased by brief pressure overload (P < 0.001), whereas c-Jun N-terminal kinase phosphorylation was significantly decreased (P < 0.001). Hemodynamics, area at risk, and mortality did not differ significantly among groups.Conclusions: Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation. (C) 2015 Elsevier Inc. All rights reserved.