Bergqvist P B, Vogels B A, Bosman D K, Maas M A, Hjorth S, Chamuleau R A, Bengtsson F
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
J Neurochem. 1995 Mar;64(3):1238-44. doi: 10.1046/j.1471-4159.1995.64031238.x.
Intracerebral microdialysis was applied to monitor the neocortical extracellular levels of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, the neurotransmitters dopamine (DA), noradrenaline (NA), and serotonin (5-HT), and the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA) in rats with various forms of experimental hepatic encephalopathy (HE). The extracellular aromatic amino acid levels were clearly increased in acute, subacute, and chronic HE. No changes compared with controls in the neocortical DA release could be detected in the three experimental HE rat models investigated. The NA release showed a significant increase only in the subacute HE group. These data suggest that HE may not be associated with any major reduction of neocortical DA or NA release as previously suggested. In acute and subacute HE, decreased extracellular DOPAC but elevated 5-HIAA concentrations were seen. In chronic HE, elevations of both DOPAC and 5-HIAA were observed. Neocortical 5-HT release did not change in subacute and chronic HE, whereas it decreased in acute HE compared with control values. Significant increase in extracellular concentrations of 5-HIAA and of the 5-HIAA/5-HT ratio in the present study are in agreement with previously reported increases in 5-HT turnover in experimental HE. However, a substantially increased 5-HT turnover in experimental HE does not appear to be related to an increase in neuronal neocortical 5-HT release.
采用脑内微透析技术监测不同形式实验性肝性脑病（HE）大鼠新皮质细胞外液中芳香族氨基酸苯丙氨酸、酪氨酸和色氨酸、神经递质多巴胺（DA）、去甲肾上腺素（NA）和5-羟色胺（5-HT）以及代谢产物3,4-二羟基苯乙酸（DOPAC）和5-羟基吲哚-3-乙酸（5-HIAA）的水平。在急性、亚急性和慢性HE中，细胞外芳香族氨基酸水平明显升高。在所研究的三种实验性HE大鼠模型中，未检测到新皮质DA释放与对照组相比有变化。NA释放仅在亚急性HE组显著增加。这些数据表明，HE可能不像之前所认为的那样与新皮质DA或NA释放的任何显著减少有关。在急性和亚急性HE中，细胞外DOPAC降低，但5-HIAA浓度升高。在慢性HE中，观察到DOPAC和5-HIAA均升高。在亚急性和慢性HE中，新皮质5-HT释放没有变化，而在急性HE中与对照值相比有所降低。本研究中细胞外5-HIAA浓度及5-HIAA/5-HT比值显著升高与先前报道的实验性HE中5-HT周转率增加一致。然而，实验性HE中5-HT周转率的显著增加似乎与新皮质神经元5-HT释放的增加无关。
