Anundi I, King J, Owen D A, Schneider H, Lemasters J J, Thurman R G
Am J Physiol. 1987 Sep;253(3 Pt 1):G390-6. doi: 10.1152/ajpgi.1987.253.3.G390.
Perfusion of livers from fasted rats with nitrogen-saturated buffer caused hepatocellular damage within 30 min. Lactate dehydrogenase (LDH) was released at maximal rates of approximately 300 U . g-1 . h-1 under these conditions, and virtually all cells in periportal and pericentral regions of the liver lobule were stained with trypan blue. Infusion of glucose, xylitol, sorbitol, or mannitol (20 mM) did not appreciably change the time course or extent of damage due to perfusion with nitrogen-saturated perfusate. However, fructose (20 mM) completely prevented damage assessed by LDH release, trypan blue uptake, and ultrastructural changes for at least 2 h of perfusion. Neither glucose, xylitol, sorbitol, nor mannitol (20 mM) increased lactate formation above basal levels during hypoxia. On the other hand, fructose (0.4-20 mM) caused a concentration-dependent increase in lactate formation that reached maximal rates of approximately 180 mumol . g-1 . h-1. The dose-dependent increase in glycolytic lactate production from fructose correlated well with cellular protection reflected by decreases in LDH release. ATP:ADP ratios were also increased from 0.4 to 1.8 in a dose-dependent manner by fructose. The results indicate that fructose protects the liver against hypoxic cell death by the glycolytic production of ATP in the absence of oxygen.
用氮气饱和的缓冲液灌注禁食大鼠的肝脏，30分钟内就会导致肝细胞损伤。在这些条件下，乳酸脱氢酶（LDH）以约300 U·g⁻¹·h⁻¹的最大速率释放，肝小叶门静脉周围和中央周围区域的几乎所有细胞都被台盼蓝染色。输注葡萄糖、木糖醇、山梨醇或甘露醇（20 mM）并没有明显改变用氮气饱和灌注液灌注所导致的损伤的时间进程或程度。然而，果糖（20 mM）在至少2小时的灌注过程中，完全防止了通过LDH释放、台盼蓝摄取和超微结构变化评估的损伤。在缺氧期间，葡萄糖、木糖醇、山梨醇或甘露醇（20 mM）均未使乳酸生成量高于基础水平。另一方面，果糖（0.4 - 20 mM）导致乳酸生成量呈浓度依赖性增加，达到约180 μmol·g⁻¹·h⁻¹的最大速率。果糖糖酵解产生乳酸的剂量依赖性增加与LDH释放减少所反映的细胞保护作用密切相关。果糖还使ATP:ADP比值以剂量依赖性方式从0.4增加到1.8。结果表明，果糖在无氧条件下通过糖酵解产生ATP来保护肝脏免受缺氧性细胞死亡。
