Yarmush D M, MacDonald A D, Foy B D, Berthiaume F, Tompkins R G, Yarmush M L
Center for Engineering in Medicine, Massachusetts General Hospital, Boston, USA.
J Burn Care Rehabil. 1999 Jul-Aug;20(4):292-302. doi: 10.1097/00004630-199907000-00004.
Severe injury induces a hypermetabolic state in the liver; however, the pathways that are responsible for the increase in hepatic energy demand have not been identified. Relative fluxes in the tricarboxylic acid (TCA) cycle were determined in perfused livers from rats 4 days after administration of a cutaneous burn injury. The perfusate was supplemented with 5 mM uniformly labeled 13C-lactate to efficiently label intracellular metabolites. Flux ratios were calculated on the basis of (1) the 13C-labeling pattern of the glutamate and lactate isotopomers within the liver as determined by nuclear magnetic resonance spectroscopy and (2) an isotopomer mass balance model of the TCA cycle. Calculated flux ratios suggest that burn injury results in an increase in the contribution of pyruvate to the oxaloacetate pool at the expense of non-TCA cycle sources. Furthermore, a dramatic increase in 13C-labeling of glucose was observed in burned rat livers. These data taken together suggest that burn injury induces intrinsic changes in intrahepatic metabolism, including an alteration of the relative fluxes consistent with increased gluconeogenesis from lactate.
严重损伤会在肝脏中诱导一种高代谢状态；然而，导致肝脏能量需求增加的途径尚未明确。在给予皮肤烧伤损伤4天后的大鼠灌流肝脏中测定了三羧酸（TCA）循环中的相对通量。向灌流液中添加5 mM均匀标记的13C-乳酸以有效标记细胞内代谢物。通量比率是基于以下两点计算得出的：（1）通过核磁共振波谱法测定的肝脏内谷氨酸和乳酸异构体的13C标记模式，以及（2）TCA循环的异构体质量平衡模型。计算得出的通量比率表明，烧伤损伤导致丙酮酸对草酰乙酸池的贡献增加，而以非TCA循环来源为代价。此外，在烧伤大鼠的肝脏中观察到葡萄糖的13C标记显著增加。综合这些数据表明，烧伤损伤会诱导肝内代谢的内在变化，包括与乳酸糖异生增加相一致的相对通量改变。
