Cell biology of ischemia/reperfusion injury.
Cell biology of ischemia/reperfusion injury.
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DOI：
10.1016/b978-0-12-394309-5.00006-7
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发表时间：
2012
影响因子：
--
通讯作者：
Korthuis, Ronald J.
中科院分区：
文献类型：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
关键词：
以缺血/再灌注（I/R）为特征的疾病，如心肌梗死、中风和周围血管疾病，仍然是导致衰弱性疾病和死亡的最常见原因之一。组织损伤和/或死亡是初始缺血损伤的结果，这主要取决于血液供应中断的程度和持续时间，然后是再灌注引起的后续损伤。在长时间缺血期间，由于无氧代谢和乳酸积累，ATP水平和细胞内pH值降低。因此，atp酶依赖的离子转运机制变得功能失调，导致细胞内和线粒体钙水平升高（钙超载），细胞肿胀和破裂，以及细胞坏死、坏死、凋亡和自噬机制导致的细胞死亡。虽然再灌注后氧水平恢复，但活性氧产生激增，促炎中性粒细胞浸润缺血组织，加剧缺血损伤。I/R诱导的病理事件协调线粒体通透性过渡孔的打开，这似乎代表了I/R引发的病理事件的共同末端执行器。这篇论文的目的是对I/R损伤发展的机制进行全面的回顾，从中可以明显看出，必须采用针对多种病理过程的分子和细胞方法的结合来限制I/R损伤的程度，以增强对细胞死亡的抵抗力和增加再生能力，从而实现缺血组织的长期修复。
Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues.