AMINO-ACID CHANGES IN AUTOPSIED BRAIN-TISSUE FROM CIRRHOTIC-PATIENTS WITH HEPATIC-ENCEPHALOPATHY
AMINO-ACID CHANGES IN AUTOPSIED BRAIN-TISSUE FROM CIRRHOTIC-PATIENTS WITH HEPATIC-ENCEPHALOPATHY
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DOI：
10.1111/j.1471-4159.1987.tb00949.x
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发表时间：
1987-09-01
影响因子：
4.7
通讯作者：
BUTTERWORTH, RF
中科院分区：
文献类型：
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作者：
LAVOIE, J;GIGUERE, JF;BUTTERWORTH, RF
尸检时，从9名死于肝性昏迷的肝硬化患者和同等数量的无神经、精神或肝脏疾病的对照组中获得脑组织，从死亡到解剖脑样本冷冻的年龄和时间间隔相匹配。谷氨酰胺，谷氨酸，天冬氨酸，还有。采用高效液相色谱荧光检测法测定大脑皮层（前额叶和额叶）、尾状核、下丘脑、小脑（皮层和蚓部）和延髓中邻苯二醛衍生物-氨基丁酸（GABA）的含量。谷氨酰胺浓度在所有大脑结构中都升高了2到4倍，在前额叶皮层和延髓中观察到最大的增加。肝硬化患者的前额皮质（20%）、尾状核（27%）和小脑蚓部（17%）的谷氨酸水平选择性降低。另一方面，这些患者尸检脑组织的GABA含量在所有脑结构中均在正常范围内。这表明谷氨酸的这种区域选择性减少可能反映了可释放（神经递质）池中氨基酸的损失。这些发现可能对慢性肝病引起的肝性脑病的发病机制有重要意义。
Brain tissue was obtained at autopsy from nine cirrhotic patients dying in hepatic coma and from an equal number of controls, free from neurological, psychiatric, or hepatic diseases, matched for age and time interval from death to freezing of dissected brain samples. Glutamine, glutamate, aspartate, and .gamma.-aminobutyric acid (GABA) levels were measured in homogenates of cerebral cortex (prefrontal and frontal), caudate nuclei, hypothalamus, cerebellum (cortex and vermis), and medulla oblongata as their o-phthalaldehyde derivatives by HPLC using fluorescence detection. Glutamine concentrations were found to be elevated two- to fourfold in all brain structures, the largest increases being observed in prefrontal cortex and medulla oblongata. Glutamate levels were selectively decreased in prefrontal cortex (by 20%), caudate nuclei (by 27%), and cerebellar vermis (by 17%) from cirrhotic patients. On the other hand, GABA content of autopsied brain tissue from these patients was found to be within normal limits in all brain structures. It is suggested that such region-selective reductions of glutamate may reflect loss of the amino acid from the releasable (neurotransmitter) pool. These findings may be of significance in the pathogenesis of hepatic encephalopathy resulting from chronic liver disease.