Mousseau D D, Butterworth R F
Neuroscience Research Unit, St-Luc Hospital, University of Montreal, Québec, Canada.
Prog Brain Res. 1995;106:277-84. doi: 10.1016/s0079-6123(08)61224-8.
In 1971 Fischer and Baldessarini proposed the hypothesis that hepatic encephalopathy (HE), a neuropsychiatric syndrome associated with hepatic dysfunction, could result from the direct decarboxylation of amino acids leading to trace amines such as tyramine and octopamine which could then act as false neurotransmitters. This was supported by the observation that the clinical symptoms of HE appeared to improve following treatment with L-Dopa, which cannot be metabolized to either of these trace amines. In addition to serum and urine levels of octopamine correlating roughly with the grade of clinical HE, levels of octopamine were also significantly increased in rat brain following coma induced by hepatic devascularization and in portacaval-shunted rats fed high aromatic amino acid content diets. This hypothesis was questioned, however, given the lack of observable adverse behavioural effects following treatments with octopamine. Finally, the equivocal results of a limited number of clinical trials (using L-Dopa) argued against a direct intervention by catecholamine-like trace amines in HE. An alternative hypothesis was advanced by Sourkes in 1978 implicating increased tryptophan metabolism as a factor in the etiology of HE. Hepatic dysfunction in humans alters CNS concentrations of tryptophan which correlate well with levels of the tryptamine metabolite indoleacetic acid (IAA). Furthermore, regional densities of [3H]tryptamine receptors in HE patient brain tissue are significantly decreased. These data support a pathophysiologic role for tryptophan and its neuroactive trace amine metabolite tryptamine in HE.
1971年，菲舍尔和巴尔迪萨里尼提出了一个假说，即肝性脑病（HE）作为一种与肝功能障碍相关的神经精神综合征，可能源于氨基酸的直接脱羧作用，从而产生酪胺和章鱼胺等痕量胺，这些痕量胺随后可作为假性神经递质发挥作用。这一假说得到了以下观察结果的支持：用左旋多巴治疗后，肝性脑病的临床症状似乎有所改善，而左旋多巴不能代谢为这两种痕量胺中的任何一种。除了章鱼胺的血清和尿液水平大致与临床肝性脑病的分级相关外，在肝血管阻断诱导昏迷的大鼠以及喂食高芳香族氨基酸含量饮食的门腔分流大鼠的大脑中，章鱼胺水平也显著升高。然而，鉴于用章鱼胺治疗后缺乏可观察到的不良行为影响，这一假说受到了质疑。最后，有限数量的临床试验（使用左旋多巴）的不明确结果也反驳了儿茶酚胺样痕量胺在肝性脑病中直接起作用的观点。1978年，索尔克斯提出了另一种假说，认为色氨酸代谢增加是肝性脑病病因中的一个因素。人类的肝功能障碍会改变中枢神经系统中色氨酸的浓度，而色氨酸浓度与色胺代谢产物吲哚乙酸（IAA）的水平密切相关。此外，肝性脑病患者脑组织中[3H]色胺受体的区域密度显著降低。这些数据支持了色氨酸及其神经活性痕量胺代谢产物色胺在肝性脑病中的病理生理作用。
