Papegay Bérengère, Stadler Michaela, Nuyens Vincent, Kruys Véronique, Boogaerts Jean G, Vamecq Joseph
Laboratory of Experimental Medicine (ULB Unit 222), University Hospital Center, Charleroi, Belgium.
Laboratory of Molecular Biology of the Gene, Department of Molecular Biology, Free University of Brussels (ULB), Gosselies, Belgium.
Nutrition. 2017 Mar;35:21-27. doi: 10.1016/j.nut.2016.10.008. Epub 2016 Oct 14.
Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting.
Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers.
Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate.
High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role.
饮食限制或减少食物摄入量被认为可预防肾和肝缺血性损伤。有鉴于此，最近有研究表明短期禁食可保护原位大鼠肝脏免受缺血再灌注损伤。在此，将离体灌注而非原位肝脏暴露于缺血再灌注中，以研究在能量底物方面使肝脏与肝外供应断开连接对短期禁食所提供保护的影响。
将短期（18小时）禁食的大鼠与喂食的大鼠的离体灌注肝脏进行缺血再灌注，并研究灌注液中细胞溶解标志物的释放情况。能量储备在时间上的可用性不同，同时还测量了肝脏在不同时间点的细胞能量电荷（三磷酸腺苷浓度加上二磷酸腺苷浓度的一半与三磷酸腺苷+二磷酸腺苷+一磷酸腺苷浓度总和的比值）、磷酸腺苷和糖原。
与喂食相比，短期禁食未能保护离体灌注的大鼠肝脏免受缺血/再灌注损伤，反而在复氧阶段增加了灌注液中细胞溶解标志物（钾、细胞色素c、天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶）的释放。短期禁食与喂食相比的毒性与肝脏中较低的糖原和能量电荷以及灌注液中较低的乳酸水平有关。
高能量电荷、糖原的细胞内含量和糖酵解活性可能保护肝脏免受缺血/再灌注损伤。这项工作并未质疑先前文献中所证明的饮食限制和短期禁食的保护作用有多大。事实上，它表明超过0.3的能量电荷阈值可能会触发这种保护作用的有效性。
