Relationship between levels of brain peptides and metabolism of ammonia and glutamate in LEC rats spontaneously develop fulminant hepatitis

本文研究了LEC大鼠脑内和血液中CCK、生长抑素、神经激肽A和B等脑肽含量与氨和谷氨酸代谢的关系。本文还观察了谷氨酸受体拮抗剂MK 801对急性氨中毒大鼠惊厥和脑内谷氨酸代谢的影响。(1)肝性脑病的程度与血氨和血浆芳香族氨基酸呈显著相关，提示LEC大鼠可作为一种新的急性肝性脑病模型。(2)结果表明，LEC肝性脑病大鼠脑水提液中CCK免疫反应性（41.5 × 2.6pmol/g湿重）明显低于无肝性脑病的LEC大鼠（67.1 × 6.9）。(3)在无肝性脑病的大鼠中，每个视野的CCK免疫反应细胞数（x125）为28.5*0.7，在III至V期肝性脑病的大鼠中为14.1*2.0。CCK免疫反应神经细胞减少， 关于我们 在I、II期肝性脑病大鼠中未观察到LLS。(4)LEC肝性脑病大鼠脑组织（下丘脑、延髓、纹状体和脊髓）生长抑素-14和生长抑素-28-（1-12）样免疫反应蛋白水平均显著低于无肝性脑病的LEC大鼠。(5)LEC肝性脑病大鼠纹状体和脊髓神经激肽B（NKB）免疫反应性水平明显低于无肝性脑病的LEC大鼠。NKB免疫反应性水平与血氨显着相关，但与血浆芳香族氨基酸水平无相关性。神经激肽A免疫反应性水平无显著降低。(6)LEC肝性脑病大鼠脑内谷氨酸和GABA含量降低，谷氨酰胺含量升高。这些数据的水平在大脑的不同部分发生变化。(7)预先给予谷氨酸受体拮抗剂MK 801的大鼠惊厥潜伏期明显短于未给予MK 801的大鼠。这些数据表明，在急性氨中毒大鼠中，MK 801可能会加速氨毒性，因为MK 801会干扰谷氨酸盐形成谷氨酰胺。少

Relationship between levels of brain peptides (CCK, somatostatin,and neurokinin A&B) and metabolism of ammonia and glutamate were studied in the brain and blood of LEC rats. Influence of glutamate receptor antagonist (MK801) on convulsion and brain metabolism of glutamate in rats with acute ammonia toxication was also examined.Following results were obtained. (1) Degree of hepatic encephalopathy significantly correlated with blood ammonia and plasma aromatic amino acids, suggesting the usefulness of LEC rats as a new model for acute hepatic encephalopathy. (2) Levels of CCK immunoreactivity (41.5*2.6pmol/g wet wt) in water extract from the brain of LEC rats with hepatic encephalopathy were significantly lower than those in LEC rats without hepatic encephalopathy (67.1*6.9). (3) Number of CCK-immunoreactive cells per field (x125) was 28.5*0.7 in rats without hepatic encephalopathy, and 14.1*2.0 in rats with stage III to V hepatic encephalopathy. A decrease in CCK-immunoreactive nerve ce … More lls was not observed in the rats with stage I or II hepatic encephalopathy. (4) Levels of both somatostatin-14-like immunoreactivity and somatostatin-28-(1-12)-like immunoreactivity in the brain (hypothalamus, medulla oblongata, striatum and spinal cord) of LEC rats with hepatic encephalopathy were significantly lower than those in LEC rats without hepatic encephalopathy. (5) Levels of neurokinin B(NKB) immunoreactivity in the striatum and spinal cord of LEC rats with hepatic encephalopathy were significantly reduced compared to those in LEC rats without hepatic encephalopathy. Levels of NKB immunoreactivity significantly correlated with blood ammonia but no correlated with levels of plasma aromatic amino acids. No significant reduction was found in levels of neurokinin A immunoreactivity. (6) Decrease in glutamate and GABA level and increase in glutamine level were observed in the brain of LEC rats with hepatic encephalopathy. Levels of these data were changed at different portion of the brain. (7) Incubation time until convulsion was significantly shorter in the rats pretreated with MK801, glutamate receptor antagonist than in rats with out 801. These data indicate that ammonia toxicity may be accelerated by MK801 which interferes in glutamine formation from glutamate in rats with acute ammonia toxication. Less