In Vivo Measurement of Ethanol Metabolism in the Rat Liver Using Magnetic Resonance Spectroscopy of Hyperpolarized [1-13C]Pyruvate
In Vivo Measurement of Ethanol Metabolism in the Rat Liver Using Magnetic Resonance Spectroscopy of Hyperpolarized [1-13C]Pyruvate
复制标题
DOI：
10.1002/mrm.21998
复制
发表时间：
2009-08-01
影响因子：
3.3
通讯作者：
Pfefferbaum, Adolf
中科院分区：
文献类型：
--
作者：
Spielman, Daniel M.;Mayer, Dirk;Pfefferbaum, Adolf
[1-C-13]丙酮酸是一种易极化底物，已成为体内代谢的众多磁共振波谱（MRS）研究的对象。在这项工作中，超极化[1-C-13]丙酮酸的C-13-MRS被用来询问既不涉及有氧代谢也不涉及无氧代谢的代谢途径。特别是，乙醇的消耗会导致肝脏代谢的改变，当过量时会导致不良的医疗状况，包括脂肪肝、肝炎、肝硬化和癌症。在这里，我们提出了一种非侵入性监测这一重要过程在体内的方法。推注超极化[1-C-13]丙酮酸盐后，我们证明了与乙醇共同给药时大鼠肝脏乳酸产生速率显著增加（P = 0.0016，非配对t检验）。这种影响归因于与乙醇代谢相关的肝脏烟酰胺腺嘌呤二核苷酸（NADH）增加，以及NADH在乳酸-乳酸转化中作为辅酶的作用。除了肝脏代谢的研究之外，这种新的体内测定NADH水平的变化使得超极化[1-C-13]丙酮酸盐成为研究使用NADH（或NAD（+））作为辅酶的多种体内代谢途径的潜在可行底物，从而拓宽了迄今为止文献中讨论的应用范围。Magn Reson Med 62：307-313，2009. (C)2009威利-利斯公司
[1-C-13]Pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work C-13-MRS of hyperpolarized [1-C-13]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-C-13]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-C-13]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date. Magn Reson Med 62:307-313, 2009. (C) 2009 Wiley-Liss, Inc.