UCL Division of Surgery and Interventional Science, University College London, London, United Kingdom.
Am J Surg. 2010 Oct;200(4):507-18. doi: 10.1016/j.amjsurg.2009.09.028. Epub 2010 Apr 21.
Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity.
New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC + IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy.
The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and β-hydroxybutarate/acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC + IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro.
This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC.
轻度至中度脂肪性肝脏被用作肝移植的边缘供体。关于脂肪肝的缺血再灌注（IRI）损伤（IRI）机制知之甚少。本研究旨在确定 COX 活性是否在脂肪肝中因 IRI 而受损，以及是否可以通过缺血预处理（IPC）来保护 COX 活性。
新西兰兔喂食高胆固醇饮食 8 周以诱导中度肝脂肪变性。测试了三组。IRI 组经历 60 分钟的缺血，随后进行 7 小时的再灌注。IPC 组（IPC+IR）经历 5 分钟的缺血，随后进行 10 分钟的再灌注，然后经历 60 分钟的缺血和 7 小时的再灌注。对照组（假手术）进行相同的手术程序，但不诱导缺血。通过近红外光谱术在体内连续监测脱氧血红蛋白、氧合血红蛋白和 COX 氧化还原状态的变化。在体外对肝活检标本进行 COX 和柠檬酸合酶（CS）活性测定。在整个过程中连续收集胆汁并通过质子核磁共振波谱进行分析。
IRI 组 COX 活性降低，脱氧血红蛋白、氧合血红蛋白、COX 代表的组织氧合作用降低，乳酸/丙酮酸和β-羟丁酸/乙酰乙酸的氧化还原比升高，体外 COX 和 CS 活性降低。IPC+IR 组体内所有测量参数水平较高，体外 COX 和 CS 活性下降较小。
本研究表明 IRI 影响脂肪肝中的 COX 活性。IPC 可减轻这种影响。
