Ischemic preconditioning increases the tolerance of fatty liver to hepatic ischemia-reperfusion injury in the rat
Ischemic preconditioning increases the tolerance of fatty liver to hepatic ischemia-reperfusion injury in the rat
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DOI：
10.1016/s0002-9440(10)64214-9
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发表时间：
2002-08-01
影响因子：
6
通讯作者：
Peralta, C
中科院分区：
文献类型：
--
作者：
Serafin, A;Roselló-Catafau, J;Peralta, C
肝脏脂肪变性是缺血再灌注的主要危险因素。本研究评估了在正常肝脏中证明有效的预处理是否也可以在脂肪变性的情况下提供保护，并调查了潜在的保护机制。与瘦大鼠相比，肥胖大鼠在缺血60分钟后肝损伤增加，存活率降低。脂肪肝表现出一定程度的中性粒细胞积聚和微循环改变类似于正常肝脏。然而，在脂肪变性的存在下，肝脏再灌注后观察到脂质过氧化反应增加，谷胱甘肽酯预处理可以减少脂质过氧化反应。缺血预处理可减轻肝损伤，提高动物存活率。在正常和脂肪肝中，发现这种内源性保护机制可以控制脂质过氧化、肝脏微循环衰竭和中性粒细胞积聚，减少随后的肝损伤。这些有益的效果可以介导的一氧化氮，因为抑制一氧化氮合成和一氧化氮供体预处理废除和模拟，分别预处理的好处。因此，缺血预处理可能是一种有效的手术策略，以减少在常温条件下的正常和脂肪肝，包括肝切除，肝移植的肝脏缺血再灌注损伤。
Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation.