Serafín Anna, Roselló-Catafau Joan, Prats Neus, Xaus Carme, Gelpí Emilio, Peralta Carmen
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Cientificas, Barcelona, Spain.
Am J Pathol. 2002 Aug;161(2):587-601. doi: 10.1016/S0002-9440(10)64214-9.
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.
肝脂肪变性是缺血再灌注的主要危险因素。本研究评估了预处理（已证实在正常肝脏中有效）在存在脂肪变性的情况下是否也能提供保护，并研究了潜在的保护机制。与瘦大鼠相比，肥胖大鼠在缺血60分钟后肝损伤增加且存活率降低。脂肪肝表现出一定程度的中性粒细胞聚集和微循环改变，与正常肝脏相似。然而，在存在脂肪变性的情况下，肝再灌注后观察到脂质过氧化增加，而谷胱甘肽酯预处理可降低脂质过氧化。缺血预处理减轻了肝损伤并提高了动物存活率。在正常肝脏和脂肪肝中，均发现这种内源性保护机制可控制脂质过氧化、肝微循环衰竭和中性粒细胞聚集，从而减轻随后的肝损伤。这些有益作用可能由一氧化氮介导，因为一氧化氮合成的抑制和一氧化氮供体预处理分别消除和模拟了预处理的益处。因此，缺血预处理可能是一种有效的手术策略，可在常温条件下减轻正常肝脏和脂肪肝的肝缺血再灌注损伤，包括肝切除术和肝移植。
