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大鼠脑和血中脑多肽(CCK、生长抑素、神经激肽A和B)水平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(MK801)对急性氨中毒大鼠惊厥及谷氨酸脑代谢的影响。(1)肝性脑病程度与血氨、血浆芳香族氨基酸显著相关，提示LEC可作为一种新的急性肝性脑病模型。(2)LEC肝性脑病大鼠脑水提物中CCK免疫活性(41.5±2.6pmol/g湿重)显著低于非肝性脑病LEC大鼠(67.1±6.9)。(3)无肝性脑病大鼠的CCK免疫反应细胞数(X125)为28.5×0.7个/视野，肝性脑病大鼠为14.1±2.0个/视野。CCK免疫反应神经Ce-…减少肝性脑病I、II期大鼠未观察到较多的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)样免疫反应均显著低于非肝性脑病LEC大鼠。(5)LEC肝性脑病大鼠纹状体和脊髓内神经激肽B(NKB)免疫反应活性较非肝性脑病LEC大鼠显著降低。NKB免疫反应性水平与血氨显著相关，与血浆芳香族氨基酸水平无相关性。神经激动素A免疫反应水平未见明显下降。(6)肝性脑病LEC大鼠脑内谷氨酸、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了变化。(7)给予谷氨酸受体拮抗剂MK801的大鼠惊厥潜伏期明显短于未给予Out 801的大鼠。提示MK801对急性氨中毒大鼠谷氨酸合成谷氨酰胺有明显的干预作用，可加速氨中毒。较少

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