Oxidative Stress and Liver Ischemia-Reperfusion Injury
Oxidative Stress and Liver Ischemia-Reperfusion Injury
复制标题
DOI：
10.1007/978-3-319-15539-5_7
复制
发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Fernandez-Checa, Jose C.
中科院分区：
文献类型：
--
作者：
Garcia-Ruiz, Carmen;Morales, Albert;Fernandez-Checa, Jose C.
肝脏缺血/再灌注 (I/R) 损伤是一种严重的并发症，由于肝细胞大量丢失，会损害肝功能，从而影响肝脏手术和肝移植等多种临床环境。尽管已经确定了几种与肝细胞死亡有关的细胞间和分子机制，其中活性氧（ROS）的产生起着主要作用，但导致肝缺血再灌注损伤的机制尚不清楚。氧气是维持生命的重要元素，但其部分还原会产生有毒的活性氧，参与肝脏缺血再灌注损伤。线粒体是细胞中 ROS 产生的主要来源之一，目前的数据表明线粒体功能障碍会介导肝 I/R 损伤。在肝移植或肝切除术中，缺血再灌注伴随着ROS生成的增加，导致肝损伤。肝脂质成分的贡献，特别是线粒体膜的脂质成分，决定了肝 I/R 期间由于线粒体抗氧化防御受损而导致 ROS 生成增加。临床和实验观察积累的证据表明，肝移植中的脂肪变性移植物会增加再灌注损伤和肝移植失败。在本章中，我们将回顾关于 I/R 后肝损伤中线粒体、ROS 生成和抗氧化防御之间相互作用的最新数据，并提供证据证明线粒体胆固醇积累在肝 I/R 损伤中发挥着重要作用，从而成为干预的新目标。
Hepatic ischemia/reperfusion (I/R) injury is a serious complication that compromises liver function because of extensive hepatocellular loss, which impacts diverse clinical settings such as liver surgery and liver transplantation. The mechanisms responsible for hepatic I/R injury are not well understood despite the identification of several intercellular and molecular mechanisms involved in the hepatocellular cell death, with a predominant role for reactive oxygen species (ROS) generation. Oxygen is a vital element to sustain life but its partial reduction generates toxic ROS that participate in liver I/R damage. Mitochondria are one of the main sources of ROS production in the cell, and current data point that mitochondrial dysfunction mediates hepatic I/R damage. In liver transplantation or in hepatic resections ischemia followed by reperfusion is accompanied by an increase in ROS generation leading to liver injury. The contribution of hepatic lipid composition, particularly lipid composition of mitochondrial membranes determine the increased ROS generation during hepatic I/R due to compromised mitochondrial antioxidant defenses. Accumulating evidence from clinical and experimental observations indicates that steatotic grafts in liver transplantation increase reperfusion injury and liver transplant failure. In this chapter we will review recent data on the interplay between mitochondria, ROS generation, and antioxidant defense in liver damage after I/R, and provide evidence that mitochondrial cholesterol accumulation stands as an important player in liver I/R damage, thus emerging as a novel target for intervention.