Bergeron M, Swain M S, Reader T A, Grondin L, Butterworth R F
André-Viallet Clinical Research Centre, Hôpital Saint-Luc, Montréal, Québec, Canada.
J Neurochem. 1990 Jul;55(1):222-9. doi: 10.1111/j.1471-4159.1990.tb08842.x.
Four weeks following portacaval anastomosis (PCA) in the rat, severe liver atrophy, sustained hyperammonemia, and increased plasma and brain tryptophan are observed. Administration of ammonium acetate (NH4Ac) to rats with PCA precipitates severe signs of hepatic encephalopathy (HE) (loss of righting reflex progressing to loss of consciousness and ultimately deep coma). To evaluate the relationship between the deterioration of neurological status in HE and serotonin (5-HT) metabolism, the levels of 5-HT, its precursor 5-hydroxytryptophan, and its major metabolite 5-hydroxy-indole-3-acetic acid (5-HIAA) were measured by HPLC with ion-pairing and electrochemical detection in three well-defined areas of the cerebral cortex: anterior cingulate, piriform and entorhinal, and frontoparietal; as well as in the caudate-putamen, the raphe nuclei, and the locus ceruleus in rats with PCA at different stages of HE, before and after injection of NH4Ac, as well as in sham-operated controls. The results demonstrate increased 5-HIAA/5-HT ratios after PCA and NH4Ac loading, suggesting increased 5-HT turnover in the brains of these animals. However, these changes do not appear to be related to the precipitation of coma as no significant difference in 5-HT turnover was observed between precoma and coma stages of HE. Increased 5-HT turnover in brain of shunted rats may be related to early symptoms of HE such as altered sleep patterns and disorders of motor coordination.
大鼠门腔静脉吻合术（PCA）四周后，可观察到严重的肝脏萎缩、持续性高氨血症以及血浆和脑内色氨酸增加。给接受PCA的大鼠注射醋酸铵（NH4Ac）会引发严重的肝性脑病（HE）症状（翻正反射丧失，进而发展为意识丧失，最终陷入深度昏迷）。为了评估HE中神经状态恶化与血清素（5-HT）代谢之间的关系，采用高效液相色谱法结合离子对和电化学检测，测定了大脑皮层三个明确区域（前扣带回、梨状和内嗅区以及额顶叶）、尾状核-壳核、中缝核和蓝斑核中5-HT、其前体5-羟色氨酸及其主要代谢产物5-羟吲哚-3-乙酸（5-HIAA）的水平，这些区域来自处于HE不同阶段的PCA大鼠，在注射NH4Ac之前和之后，以及假手术对照组。结果表明，PCA和NH4Ac负荷后5-HIAA/5-HT比值增加，表明这些动物大脑中5-HT周转率增加。然而，这些变化似乎与昏迷的发生无关，因为在HE的昏迷前期和昏迷期之间未观察到5-HT周转率的显著差异。分流大鼠大脑中5-HT周转率增加可能与HE的早期症状有关，如睡眠模式改变和运动协调障碍。
