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

LEC大鼠自发性暴发性肝炎脑肽水平与氨、谷氨酸代谢的关系

基本信息

批准号：
03670375
负责人：
SATO Shunichi
金额：
$ 1.22万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670375/
关键词：
fulminant hepatitis hepatic encephalopathy LEC rat brain peptide CCK neurokinin A&B amino acid ammonia CLK neurokinin A&B somatostatin

项目摘要

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

研究了LEC大鼠脑及血中CCK、生长抑素、神经激肽a和b水平与氨、谷氨酸代谢的关系。研究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。得到以下结果：(1)肝性脑病程度与血氨和血浆芳香族氨基酸显著相关，提示LEC大鼠可作为急性肝性脑病的新模型。(2)肝性脑病LEC大鼠脑水提物CCK免疫反应性（41.5*2.6pmol/g wet wt）明显低于非肝性脑病LEC大鼠（67.1*6.9）。(3)无肝性脑病大鼠cck免疫反应细胞数（x125）为28.5*0.7，III ~ V期肝性脑病大鼠为14.1*2.0。肝性脑病ⅰ、ⅱ期大鼠cck免疫反应性神经ce降低，肝性脑病ⅰ、ⅱ期大鼠未见更多的细胞凋亡。(4)肝性脑病LEC大鼠大脑（下丘脑、延髓、纹状体和脊髓）中生长抑素-14样免疫反应和生长抑素-28-(1-12)样免疫反应水平均显著低于非肝性脑病LEC大鼠。(5)肝性脑病LEC大鼠纹状体和脊髓中神经激肽B（neurokinin B， NKB）免疫反应性水平明显低于非肝性脑病LEC大鼠。NKB免疫反应性水平与血氨水平显著相关，而与血浆芳香氨基酸水平无相关性。未发现神经激肽A免疫反应性水平显著降低。(6)肝性脑病LEC大鼠脑内谷氨酸、GABA水平降低，谷氨酰胺水平升高。这些数据的水平在大脑的不同部位发生了变化。(7)谷氨酸受体拮抗剂MK801预处理大鼠的惊厥潜伏期明显短于未处理的大鼠。这些数据表明，MK801可能会干扰急性氨中毒大鼠的谷氨酸生成谷氨酰胺，从而加速氨毒性。少