Experimental Study on The Alteration of Brain Cholinergic Neurotransmitter System in Hepatic Encephalopathy

肝性脑病脑胆碱能神经递质系统改变的实验研究

• 批准号: 06670579
• 负责人: SUZUKI Kazuyuki
• 金额: $ 0.32万
• 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: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670579/
• 关键词: Hepatic encephalopathy; Acute hepatic failure; Chronic hepatic failure; Acethylcholine; Monoamine; Ammonia; Neurotransmitter

To investigate the alteration of cholinergic neurotransmitter (acethylcholine ; ACh) system in hepatic encephalopathy, we measured the concentration of choline (Ch) and ACh in six brain regions (frontal cortex, striatum, hipocampus, hypothalamus, midbrain, and medulla oblongata) in acute hepatic failure (AHF) mice induced by oral administration of thioacetamide (100mg/kg), and also evaluated these levels in the striatum of chronic hepatic failure (CHF) rat by microdialysis system in vivo. CHF with hyperammonemia was induced by porta-caval anastomosis and continuous load of ammonium acetate into caecum using osmotic pump. In AHF mice, Ch and ACh levels were significantly decreased in most brain regions, while significantly increased in monoaminergic metabolites in all brain areas. ACh levels showed a negative correlation with those of 5-HIAA.On the other hand, in CHF rat, Ch levels in the striatum were significantly decreased. But ACh levels were significantly increased. These results suggest that, although the braincholinergic neurotransmitter system is disturbed in hepatic encephalopathy, the levels of ACh may be altered due to the type of hepatic encephalopathy and blood ammonia levels. Further studies are needed to determine whether ACh is involved in the mechanism of hepatic encephalopathy.

为探讨胆碱能神经递质(乙酰胆碱，ACh)系统在肝性脑病中的变化，我们测定了硫代乙酰胺(100 mg/kg)诱导的急性肝功能衰竭(AHF)小鼠额叶皮质、纹状体、海马区、下丘脑、中脑和延髓6个脑区胆碱能神经递质(ACh)和胆碱能神经递质(CH)的浓度，并用微透析法测定了慢性肝功能衰竭(CHF)大鼠纹状体中胆碱和ACh的含量。门腔吻合加盲肠内持续负荷醋酸铵诱导高氨血症CHF模型。在AHF小鼠中，大多数脑区的CH和ACh水平显著降低，而所有脑区单胺类代谢物的水平显著增加。ACh水平与5-HIAA水平呈负相关，而CHF大鼠纹状体内CH水平显著降低。但ACh水平显著升高。这些结果提示，尽管肝性脑病时脑胆碱能神经递质系统受到干扰，但由于肝性脑病的类型和血氨水平的不同，ACh水平也可能发生改变。ACh是否参与肝性脑病的发病机制尚需进一步研究。

项目成果

Masakatsu Iwai, et al: "Decresed brain concentrations of choline and ecetylcholine in mice with thioacetamide-induced acute liver failure." Int. Henatol. Comm.3. 222-226 (1995)

Masakatsu Iwai 等人：“硫代乙酰胺诱导的急性肝衰竭小鼠脑内胆碱和乙酰胆碱浓度降低。”

Masakatsu Iwai, Kazuyuki Suzuki, et al.: "Decreased brain concentrations of choline and acethylcholine in mice with thioacetamide-induced acute liver failure." Int.Hepatol.Comm.3. 222-226 (1995)

Masakatsu Iwai、Kazuyuki Suzuki 等人：“硫代乙酰胺诱导的急性肝衰竭小鼠脑内胆碱和乙酰胆碱浓度降低。”

岩井正勝、他: "チオアセトアミド負荷急性肝不全マウスにおける脳内アセチルコリン、モノアミン代謝" 肝臓. 36(印刷中). (1995)

Masakatsu Iwai 等人：“硫代乙酰胺负载的急性肝衰竭小鼠的脑内乙酰胆碱和单胺代谢”36（出版中）。

岩井正勝、他: "チオアセトアミド負荷急性肝不全マウスにおける脳内アセチルコリン,モノアミン代謝" 肝臓. 36. 199-207 (1995)

Masakatsu Iwai 等人：“硫代乙酰胺负载的急性肝功能衰竭小鼠的脑内乙酰胆碱和单胺代谢”肝脏。 36. 199-207 (1995)

Masakatsu Iwai,et al: "Decreased brain concentration of choline and acetylcholin in mice with thioacetamide-induced acute liver failure" International Hepatology Communications. 3(in press). (1995)

Masakatsu Iwai 等人：“硫代乙酰胺诱导的急性肝衰竭小鼠脑内胆碱和乙酰胆碱浓度降低”国际肝病学通讯。