MONOAMINES AND METABOLITES IN AUTOPSIED BRAIN-TISSUE FROM CIRRHOTIC-PATIENTS WITH HEPATIC-ENCEPHALOPATHY
MONOAMINES AND METABOLITES IN AUTOPSIED BRAIN-TISSUE FROM CIRRHOTIC-PATIENTS WITH HEPATIC-ENCEPHALOPATHY
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DOI：
10.1007/bf00964814
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发表时间：
1989-09-01
影响因子：
4.4
通讯作者：
BUTTERWORTH, RF
中科院分区：
文献类型：
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作者：
BERGERON, M;READER, TA;BUTTERWORTH, RF
单胺神经递质代谢的改变已被认为参与了与实验性和人类肝衰竭相关的肝性脑病（HE）的发展。为了评估这一假设，在尾状核（CAU）、前额叶（PFCo）和额叶皮质（FCo）的匀浆中测量单胺及其一些代谢物，所述匀浆是从尸检获得的脑中获得的，所述尸检获得自9名死于肝昏迷的癫痫患者和相同数量的对照受试者，所述对照受试者没有神经、精神和肝脏疾病，年龄和从死亡到冷冻的时间间隔相匹配的尸检大脑样本。一元胺的测量进行了高效液相色谱与离子配对和电化学检测后，一个简单的提取程序。在研究的所有三个区域中，与对照组相比，帕金森病患者的多巴胺（DA）浓度没有变化，而其代谢产物3-甲氧基酪胺（3-MT）和高香草酸（HVA）则选择性地受到影响，即3-MT在CAU中增加，而HVA水平在FCo和CAU中增加。DOPAC在CAU中也未发生变化。去甲肾上腺素（NA）水平显着增加PFCO和FCO的患者，但在CAU保持不变。没有显着差异，无论是血清素（5-HT）或其前体5-羟色氨酸（5-HTP）的浓度被发现在任何三个地区的研究。而5-HT的主要代谢产物5-羟吲哚乙酸（5-HIAA）在癫痫患者的PFCo和CAU中升高。这些结果表明，选择性改变的儿茶酚胺和5-羟色胺系统参与人类HE，因此，他们可能发挥重要作用，在某些神经系统症状的发病机制与这种脑病。
Alterations in the metabolism of monoamine neurotransmittes have been proposed to be involved in the development of the hepatic encephalopathy (HE) associated with experimental and human liver failure. In order to evaluate this hypothesis, the monoamines and some of their metabolites were measured in homogenates of caudate nucleus (CAU), prefrontal (PFCo) and frontal cortex (FCo) dissected from brains obtained at autopsy from nine cirrhotic patients who had died in hepatic coma and an equal number of control subjects, free from neurological, psychiatric and hepatic disorders, matched for age and time interval from death to freezing of autopsied brain samples. Monoamine measurements were performed by high-performance liquid chromatography with ion-pairing and electrochemical detection after a simple extraction procedure. In all three regions investigated, concentrations of dopamine (DA) were unchanged in cirrhotic patients vs controls while its metabolites, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) were selectively affected i.e. 3-MT was found to be increased in CAU, while HVA levels were increased in FCo and CAU. DOPAC was also found to be unchanged in CAU. Noradrenaline (NA) levels were greatly increased in PFCo and FCo of cirrhotic patients but remained unchanged in CAU. No significant differences in the concentrations of either serotonin (5-HT) or of its precursor 5-hydroxytryptophan (5-HTP) were found in any of the three regions studied. However, 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of 5-HT, was increased in PFCo and CAU of cirrhotic patients. These findings show that selective alterations of catecholamine and 5-HT systems are involved in human HE and therefore, they may play an important role in the pathogensis of certain neurological symptoms associated with this encephalopathy.