Differential regulation of apoptosis by ischemia-reperfusion and ischemic adaptation.
Differential regulation of apoptosis by ischemia-reperfusion and ischemic adaptation.
复制标题
缺血再灌注和缺血适应对细胞凋亡的差异调节。
DOI：
10.1111/j.1749-6632.1999.tb09254.x
复制
发表时间：
1999
影响因子：
5.2
通讯作者：
Galang,N
中科院分区：
文献类型：
--
作者：
Maulik,N;Sasaki,H;Galang,N
摘要：缺血再灌注对心脏造成损伤，表现为心肌梗死、缺血后心室功能障碍、心律失常、心肌细胞凋亡等。通过使心脏经历短期缺血和再灌注的非致命性周期性发作，心脏可以适应缺血再灌注损伤。适应的心肌对随后的致命性缺血性损伤具有抵抗力。活性氧和氧化应激在缺血再灌注损伤的病理生理学中起着至关重要的作用。与未适应的心脏相比，适应的心脏在经历随后的缺血和再灌注时产生的氧自由基量减少。在经历缺血和再灌注的适应性心脏中，经历细胞凋亡的心肌细胞数量减少。与未适应的心脏相比，适应的心肌与抗氧化基因 Bcl-2 的增加、核转录因子 NFκB 的结合活性的增加以及 AP-1 的结合活性的降低有关。然而，当未适应的心脏遭受缺血和再灌注时，Bcl-2 下调，而 NFκB 中度上调，AP-1 显着上调。
Abstract:Ischemia and reperfusion injure the heart, as manifested by myocardial infarction, postischemic ventricular functional dysfunctions, arrhythmias, and cardiomyocyte apoptosis. Hearts can be adapted to ischemicreperfusion injury by subjecting them to non‐lethal cyclic episodes of shortterm ischemia and reperfusion. The adapted myocardium becomes resistant to subsequent lethal ischemic injury. Reactive oxygen species and oxidative stress play crucial roles in the pathophysiology of ischemic‐reperfusion injury. The adapted hearts, when subjected to subsequent ischemia and reperfusion, generate a reduced amount of oxygen free radicals compared to the nonadapted hearts. The number of cardiomyocytes undergoing apoptotic cell death is reduced in the adapted hearts subjected to ischemia and reperfusion. In concert, the adapted myocardium is associated with increased antioxidant gene Bcl‐2, increased binding activity of the nuclear transcription factor NFκB, and reduced binding activity of AP‐1 compared to nonadapted hearts. Yet when nonadapted hearts are subjected to ischemia and reperfusion, Bcl‐2 is downregulated while NFκB is moderately upregulated and AP‐1 is significantly upregulated.