Bates T E, Williams S R, Kauppinen R A, Gadian D G
Department of Physics in Relation to Surgery, Hunterian Institute, Royal College of Surgeons of England, London.
J Neurochem. 1989 Jul;53(1):102-10. doi: 10.1111/j.1471-4159.1989.tb07300.x.
Acute liver failure was induced in rats by a single intragastric dose of carbon tetrachloride. This causes hepatic centrilobular necrosis, as indicated by histological examinations, and produces a large increase in the activity of serum alanine aminotransferase. The plasma NH4+ level (mean +/- SEM) was 123 +/- 10 microM in the control group and 564 +/- 41 microM in animals with acute liver failure (each n = 5). 31P nuclear magnetic resonance (NMR) was used to monitor brain cortical high-energy phosphate compounds, Pi, and intracellular pH. 1H NMR spectroscopy was utilised to detect additional metabolites, including glutamate, glutamine, and lactate. The results show that the forebrain is capable of maintaining normal phosphorus energy metabolite ratios and intracellular pH despite the metabolic challenge by an elevated blood NH4+ level. There was a significant increase in the brain glutamine level and a concomitant decrease in the glutamate level during hyperammonaemia. The brain lactate level increased twofold in rats with acute liver failure. The results indicate that 1H NMR can be used to detect cerebral metabolic changes in this model of hyperammonaemia, and our observations are discussed in relation to compartmentation of NH4+ metabolism.
通过单次胃内给予四氯化碳在大鼠中诱导急性肝衰竭。组织学检查表明，这会导致肝小叶中心坏死，并使血清丙氨酸转氨酶活性大幅增加。对照组血浆NH4+水平（均值±标准误）为123±10微摩尔/升，急性肝衰竭动物组为564±41微摩尔/升（每组n = 5）。采用31P核磁共振（NMR）监测脑皮质高能磷酸化合物、无机磷（Pi）和细胞内pH值。利用1H NMR光谱检测其他代谢物，包括谷氨酸、谷氨酰胺和乳酸。结果表明，尽管血液NH4+水平升高带来代谢挑战，但前脑仍能够维持正常的磷能量代谢物比率和细胞内pH值。高氨血症期间，脑谷氨酰胺水平显著升高，谷氨酸水平随之降低。急性肝衰竭大鼠的脑乳酸水平增加了两倍。结果表明，1H NMR可用于检测该高氨血症模型中的脑代谢变化，并结合NH4+代谢的区室化对我们的观察结果进行了讨论。
