Hypoxic liver injury and the ameliorating effects of fructose: the "glucose paradox" revisited.
Hypoxic liver injury and the ameliorating effects of fructose: the "glucose paradox" revisited.
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缺氧性肝损伤和果糖的改善作用：重新审视“葡萄糖悖论”。
DOI：
10.1152/ajpgi.1992.263.3.g293
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Gollan,JL
中科院分区：
文献类型：
--
作者：
Brass,CA;Crawford,JM;Narciso,J;Gollan,JL
已经独立地假设营养状况是对缺氧的肝损伤反应的调节剂，并且葡萄糖可能是肝细胞代谢的不良底物。这项研究提供的数据，这两个概念的框架内的代谢分区的肝脏。使用缺氧灌注离体大鼠肝脏模型，细胞损伤，如天冬氨酸转氨酶（AST）释放所反映的，在禁食（3 h时平均AST 489 U/g肝脏）的肝脏中显著大于进食（40 U/g）动物。缺氧期间的损伤程度在用威斯康星州溶液（27 U/g）或20 mM果糖（51 U/g）灌注的禁食肝脏中降低到相当的程度。用（11.5 mM）葡萄糖加胰岛素灌注未提供肝保护（791 U/g）;然而，超生理量的葡萄糖（100 mM）与（310 U/g）或不与（321 U/g）胰岛素（10 U）或二羟丙酮（220 U/g）一起提供AST释放的适度减少。台盼蓝摄取测量的细胞损伤显示出明显的带状模式，上游区域比下游区域发生更大的实质和非实质损伤。这些数据表明，外源性葡萄糖是不良利用的能量底物的肝脏在缺氧与禁食大鼠模型的数据是一致的，表明在肝脏中的“葡萄糖悖论”。研究结果还表明，低氧水平是介导“缺氧”肝损伤的重要因素。
It has been independently postulated that nutritional status is a modulator of the hepatic injury response to hypoxia and that glucose may be a poor substrate for hepatocellular metabolism. This study provides data linking these two concepts within the framework of metabolic zonation of the liver. With the use of a hypoxically perfused isolated rat liver model, cellular injury, as reflected by aspartate aminotransferase (AST) release, was significantly greater in the liver of fasted (mean AST 489 U/g liver at 3 h) than fed (40 U/g) animals. The extent of injury during hypoxia was decreased to a comparable degree in fasted livers perfused with Wisconsin solution (27 U/g) or 20 mM fructose (51 U/g). Perfusion with (11.5 mM) glucose plus insulin provided no hepatoprotection (791 U/g); however, supraphysiological amounts of glucose (100 mM) with (310 U/g) or without (321 U/g) insulin (10 U) or dihydroxyacetone (220 U/g) provided a modest reduction in AST release. Cellular injury measured by trypan blue uptake showed a marked zonal pattern, with upstream regions incurring greater parenchymal and nonparenchymal injury than downstream areas. These data that indicate that exogenous glucose is poorly utilized as an energy substrate by the liver during hypoxia are consistent with data from the fasted-refed rat model, suggesting a "glucose paradox" in the liver. The findings also suggest that low levels of oxygen are an important factor mediating "hypoxic" liver injury.