Harvey P J, Gready J E, Hickey H M, Le Couteur D G, McLean A J
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, ACT 0200, Australia.
NMR Biomed. 1999 Oct;12(6):395-401. doi: 10.1002/(sici)1099-1492(199910)12:6<395::aid-nbm568>3.0.co;2-m.
NMR spectroscopy was used to examine hepatic metabolism in cirrhosis with a particular focus on markers of functional cellular hypoxia. (31)P and (1)H NMR spectra were obtained from liver extracts from control rats and from rats with carbon tetrachloride-induced cirrhosis. A decrease of 34% in total phosphorus content was observed in cirrhotic rats, parallelling a reduction of 40% in hepatocyte mass as determined by morphometric analysis. Hypoxia appeared to be present in cirrhotic rats, as evidenced by increased inorganic phosphate levels, decreased ATP levels, decreased ATP:ADP ratios (1.72 +/- 0.40 vs 2.48 +/- 0.50, p < 0.01), and increased inorganic phosphate:ATP ratios (2.77 +/- 0.48 vs 1.62 +/- 0.24, p < 0.00001). When expressed as a percentage of the total phosphorus content, higher levels of phosphoethanolamine and lower levels of NAD and glycerophosphoethanolamine were detected in cirrhotic rats. Cirrhotic rats also had increased phosphomonoester:phosphodiester ratios (5.73 +/- 2.88 vs 2.53 +/- 0.52, p < 0.01). These findings are indicative of extensive changes in cellular metabolism in the cirrhotic liver, with many findings attributable to the presence of intracellular hypoxia.
核磁共振波谱法用于研究肝硬化患者的肝脏代谢，特别关注功能性细胞缺氧的标志物。从对照大鼠和四氯化碳诱导的肝硬化大鼠的肝脏提取物中获得了（31）P和（1）H核磁共振谱。肝硬化大鼠的总磷含量下降了34%，与形态计量分析确定的肝细胞质量减少40%平行。肝硬化大鼠似乎存在缺氧，表现为无机磷酸盐水平升高、ATP水平降低、ATP:ADP比值降低（1.72±0.40对2.48±0.50，p<0.01）以及无机磷酸盐:ATP比值升高（2.77±0.48对1.62±0.24，p<0.00001）。以总磷含量的百分比表示时，在肝硬化大鼠中检测到较高水平的磷酸乙醇胺以及较低水平的NAD和甘油磷酸乙醇胺。肝硬化大鼠的磷酸单酯:磷酸二酯比值也升高（5.73±2.88对2.53±0.52，p<0.01）。这些发现表明肝硬化肝脏中的细胞代谢发生了广泛变化，许多发现归因于细胞内缺氧的存在。
