Neuronal and glial marker proteins in encephalopathy associated with acute liver failure and acute hyperammonemia in the rabbit
Neuronal and glial marker proteins in encephalopathy associated with acute liver failure and acute hyperammonemia in the rabbit
复制标题
兔急性肝衰竭和急性高氨血症相关脑病中的神经元和神经胶质标记蛋白
DOI：
10.1007/bf00996892
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发表时间：
1993
影响因子：
3.6
通讯作者：
K. Haglid
中科院分区：
文献类型：
--
作者：
M. Groeneweg;R. J. Knegt;A. Hamberger;M. Ding;Shu Wang;S. Schalm;K. Haglid
定量神经元和神经胶质细胞标记蛋白，以评估急性肝衰竭和急性高氨血症兔脑中蛋白水解增加的可能性。急性肝衰竭是由两阶段断流术引起的。通过长时间输注乙酸铵诱导急性高氨血症，乙酸铵模拟急性肝衰竭时的血浆氨水平。对照动物接受醋酸钠/钾输注。严重脑病发生后，处死动物（急性肝衰竭兔为13.7 ± 1.3小时，高氨血症兔为20.2 ± 0.8小时）（x ± S.E.M./ n=6），解剖大脑皮质、海马、小脑和脑干。测定总蛋白含量和神经元细胞标记蛋白NSE（神经元特异性烯醇化酶）、NF 68和NF 200（68 kD和200 kD神经丝多肽）以及胶质细胞标记蛋白GFAP（胶质细胞酸性蛋白）和S-100的浓度。仅急性高氨血症时脑干总蛋白含量降低。神经元和神经胶质细胞标记物的含量在两种条件下均不受影响。然而，在两个实验组的6只动物中的3只的海马中观察到NF 68 kD多肽的低分子量蛋白水解片段。没有观察到GFAP的蛋白水解降解。结果表明，在急性肝衰竭和急性高氨血症引起的实验性脑病中，标记蛋白没有发生重大变化。NF 68多肽的蛋白水解片段的发现表明神经元群体在神经胶质改变之前受到影响。这些发现与急性肝性脑病是可逆的并且仅引起轻微的结构变化的概念一致。
Neuronal and glial cell marker proteins were quantified in order to evaluate the possibility of increased proteolysis in the brain of rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced by a two-stage devascularization procedure. Acute hyperammonemia was induced by a prolonged infusion of ammonium acetate, which simulates the plasma ammonia level in acute liver failure. Control animals received an infusion of sodium/potassium acetate. After development of severe encephalopathy, the animals were sacrificed (13.7 ± 1.3 hours for rabbits with acute liver failure and 20.2 ± 0.8 hours for rabbits with hyperammonemia) (x ± S.E.M./n=6) and their brains were dissected into cerebral cortex, hippocampus, cerebellum and brain stem. The total protein content and the concentrations of the neuronal cell marker proteins NSE (neuron specific enolase), NF68 and NF200 (68 kD and 200 kD neurofilament polypeptides) and the glial cell marker proteins GFAP (glial fibrillary acidic protein) and S-100 were determined. Total protein content was decreased in the brain stem in acute hyperammonemia only. The content of neuronal and glial cell markers was not affected in either of the two conditions. However, low molecular weight proteolytic fragments of the NF 68 kD polypeptide were observed in the hippocampus of three out of six animals in both experimental groups. No proteolytic degradation of GFAP was observed. The results show that, in experimental encephalopathy due to acute liver failure and acute hyperammonemia, no major changes occur in the marker proteins. The finding of proteolytic fragments of the NF68 polypeptide indicates that the neuronal population is affected prior to glial alterations. These findings are in agreement with the concept that acute hepatic encephalopathy is reversible and induces only slight structural changes.