高血氨诱导肝性脑病发生发展的研究现状

摘要/Abstract

摘要： 肝性脑病（hepatic encephalopathy，HE）是急、慢性肝衰竭的严重并发症，以星形胶质细胞病变为主要病理变化。肝性脑病的发病可能与多种因素有关，大量研究表明氨在HE发病过程中起关键作用。高血氨诱导星形胶质细胞上末梢型苯二氮类受体（peripheral-type benzodiazepine receptor，PTBR）、葡萄糖转运体-1 （glucose tranporter-1，GLUT-1）、水通道蛋白-4 （aquaporin-4，AQP4）和Na⁺/K⁺-ATPase基因表达上调；影响微管相关蛋-2 （microtubule-associated protein-2，MAP-2）磷酸化及N-甲基-D-天冬氨酸（N-methyl-D-aspartate，NMDA）受体表达；诱导一氧化氮（nitricoxide，NO）合成增加从而改变神经细胞功能。此外，氨能使脑内哇巴因类复合物生成增加，并能够使Na⁺/K⁺-ATPase的活性增加。对上述因素的研究将帮助我们理解氨诱导星形胶质细胞功能障碍的基本机制，并进一步制定防治肝性脑病的新策略。

关键词: 肝性脑病, 末梢型苯二氮类受体, 葡萄糖转运体-1, 水通道蛋白-4, 钠/钾-ATPase, 微管相关蛋白2, N-甲基-D-天冬氨酸受体, 一氧化氮

Abstract: Hepatic encephalopathy （HE） is a serious complication of acute or chronic liver failure，caused by many reasons （i.e. ammonia，multiple neurotoxins，false neurotransmitters and benzodiazepine-like compounds）. Evidences suggest that ammonia plays a major role in pathogenesis of HE. Hyperammonia up-regulates gene expression of peripheral-type benzodiazepine receptor （PTBR），glucose tranporter-1 （GLUT-1），aquaporin-4 （AQP4），and Na⁺/K⁺-ATPase in astrocytes；alters the phosphorylation state of the microtubule-associated protein-2 （MAP-2） and the expression of N-methyl-D-aspartate （NMDA） receptor；induces increase of NO，therefore astrocytic disfunction. It was reported previously that ammonia increased production of ouabain-like compounds and Na⁺/K⁺-ATPase activity in astrocytes. Research to the relationship of these factors will help us to understand the underlying mechanisms of ammonia-induced astrocytic disfunction and eventually contribute to the new strategies of prevention and therapy of HE.

Key words: hepatic encephalopathy （HE）, peripheral-type benzodiazepine receptor（PTBR）, glucose tranporter-1（GLUT-1）, aquaporin-4（AQP4）, Na⁺/K⁺-ATPase, microtubule-associated protein（MAP-2）, N-methyl-D-aspartate （NMDA） receptor, nitric oxide （NO）

中图分类号:

薛占霞, 彭亮. 高血氨诱导肝性脑病发生发展的研究现状[J]. 神经药理学报, 2011, 1(4): 33-41.

XUE Zhan-xia, PENG Liang. Research Progress on Hyperammonia-induced Hepatic Encepha-lopathy[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(4): 33-41.

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