IMPORTANCE OF ASTROGLIA IN HEPATIC ENCEPHALOPATHY, FROM A PATHOPHYSIOLOGICAL ASPECT

从病理生理学角度看星形胶质细胞在肝性脑病中的重要性

• 批准号: 61570342
• 负责人: UKIDA Minoru
• 金额: $ 1.28万
• 依托单位: Okayama 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: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570342/
• 关键词: glutamine; ammonia; hepatic encephalopathy; heavy nitrogen; 重窒素; 肝不全; グルタミン; 分枝鎖アミノ酸; 高アンモニア血症; カルシウムイオン; 脳性脳症; アンモニア代謝; グルタミン酸; GC; MS; 臓器相関; グルタミン代謝; グルタミン酸代謝; ガスクロマトグラフィー質量分析

In hyperammonemic state, glutamine accumulates in the brain to high level without increase of glutamate. Using beagle dogs treated with portacaval anastomosis (PCA), we observed that infused ammonia decreased the concentration of glutamate in cerebrospinal fluid before PCA but significantly increased 4 weeks after PCA. These observation suggests that glutamine synthesis in PCA-dog brain after the load of ammonia is limited due to long standing hyperammonemia. To test this hypothesis, we measured ^<15>N enrichment of CSF glutamate and -amino N of glutamine after continuous intravenous infusion of ^<15>N-ammonium chloride (0.6 mmol/min of ^<15>N-ammonium chloride). Infusion was stopped when the animal fell into coma.The results were; during the coma state, ^<15>N was incorporated into glutamine- -amino N at the ratio of 5.2 atom% excess compared with only 0.9 atom% excess into glutamate in normal dogs, in contrast, in PCA-dogs, those were 3.7 atom% into glutamine- -amino N and 2.0 atom% into glutamate. These data strongly suggest that some disturbance in the process of glutamine synthesis in astroglia.

在高氨血症状态下，谷氨酰胺在脑中积累到高水平，而谷氨酸不增加。用门腔静脉吻合术（PCA）治疗的比格犬，我们观察到，注入氨PCA前降低脑脊液中谷氨酸的浓度，但PCA后4周显着增加。这些观察结果表明，由于长期存在的高氨血症，氨负荷后PCA-犬脑中谷氨酰胺的合成受到限制。为了验证这一假设，我们测量了<15>连续静脉输注^<15>N-氯化铵（0.6 mmol/min的^N-<15>氯化铵）后CSF谷氨酸盐的^ N富集和谷氨酰胺的-氨基N。结果表明，在昏迷状态下，<15>正常犬中，谷氨酰胺-氨基N中的^ N过量5.2原子%，谷氨酸中的^ N过量0.9原子%，而PCA犬中，谷氨酰胺-氨基N中的^N过量3.7原子%，谷氨酸中的^N过量2.0原子%。这些数据有力地表明，在星形胶质细胞的谷氨酰胺合成过程中的一些干扰。

项目成果

Y.MORIMOTO;M.UKIDA;T.TSUJI: "DYNAMIC RELATIONSHIP BETWEEN UREA AND GLUTAMINE SYNTHESIS IN THE MECHANISM OF AMMONIA DETOXICATION" Gastroenterol Jpn. 23. 538-545 (1988)

Y.MORIMOTO;M.UKIDA;T.Tsuji：“氨解毒机制中尿素和谷氨酰胺合成之间的动态关系”Gastroenterol Jpn。

M.Ukida.: Adv.Ammonia Metabolizm and Hepatic Ercephalopathy. 6. 433-438 (1988)

M.Ukida.：Adv.氨代谢和肝性脑病。

H. Morishita;M. Ukida;Y. Morimoto;H. Usui;T. Tsuji: Proc. Jap. Soc. Med. Mass Spectrom.12. 157-160 (1987)

H.森下；M.

M.UKIDA;H.MORISHITA;Y.MORIMOTO;H.USUI;H.NAGASHIMA: "LIMITED GLUTAMINE SYNTHESIS IN BRAINS OF DOGS WITH A PORTACAVAL ANASTO-MOSIS AFTER ^<15>NH_4C1 LOADING" Adv in Ammonia Metabolism and Hepatic Encephalopathy. 6. 433-438 (1988)

M.UKIDA;H.MORISHITA;Y.MORIMOTO;H.USUI;H.NAGASHIMA：“在 ^<15>NH_4C1 加载后，门静脉吻合狗大脑中谷氨酰胺的合成有限”氨代谢和肝性脑病方面的进展。

Y.Morimoto.: Gastroenterol Jpn. 23. 538-545 (1988)

Y.Morimoto.：胃肠病学日本。