Mousseau D D, Butterworth R F
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Proc Soc Exp Biol Med. 1994 Sep;206(4):329-44. doi: 10.3181/00379727-206-43770.
Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of both acute and chronic liver disease. Several hypotheses have emerged following the development of appropriate animal models of HE and following studies using postmortem brain tissue from HE patients. It was originally suggested that primary energy failure was responsible for HE; however, there is now mounting evidence that the pathogenetic defect involves neurotransmission failure. Specific neurotransmitter systems implicated in the pathogenesis of portal-systemic encephalopathy (PSE) include the excitatory amino acid glutamate as well as neuroactive and/or neurotoxic biogenic amine metabolites. Although it has been proposed that alterations in the gamma-aminobutyric acid (GABA) system may play a pathogenic role in HE associated with both chronic and acute liver failure, there is now overwhelming evidence to the contrary. On the other hand, there is evidence to suggest that a subgroup of patients with HE have increased blood and CSF concentrations of substances that bind to GABA-related benzodiazepine receptors in brain. Alterations of both the glutamatergic and serotoninergic neurotransmitter systems in PSE likely result from the metabolic consequences of chronic exposure of brain to toxic levels of ammonia. In addition to its effects on glutamatergic and serotoninergic systems during chronic liver disease, ammonia has been intimately associated with the brain edema invariably observed in acute liver failure. It is evident that, regardless of the type of liver failure, effective reductions of ammonia levels remains the strategy of choice in the prevention of encephalopathy. The further elucidation of neurotransmitter alterations in HE could result in novel "downstream" neuropharmacologic approaches to its prevention and treatment.
肝性脑病（HE）是急慢性肝病的一种严重神经精神并发症。随着合适的HE动物模型的建立以及对HE患者尸检脑组织的研究，出现了几种假说。最初有人认为原发性能量衰竭是HE的病因；然而，现在越来越多的证据表明，发病机制缺陷涉及神经传递功能障碍。与门体性脑病（PSE）发病机制相关的特定神经递质系统包括兴奋性氨基酸谷氨酸以及神经活性和/或神经毒性生物胺代谢产物。尽管有人提出γ-氨基丁酸（GABA）系统的改变可能在与慢性和急性肝衰竭相关的HE中起致病作用，但现在有大量证据表明情况恰恰相反。另一方面，有证据表明，一部分HE患者血液和脑脊液中与脑中GABA相关苯二氮䓬受体结合的物质浓度升高。PSE中谷氨酸能和5-羟色胺能神经递质系统的改变可能是由于大脑长期暴露于毒性水平的氨所导致的代谢后果。除了在慢性肝病期间对谷氨酸能和5-羟色胺能系统产生影响外，氨还与急性肝衰竭中总是出现的脑水肿密切相关。显然，无论肝衰竭的类型如何，有效降低氨水平仍然是预防脑病的首选策略。对HE中神经递质改变的进一步阐明可能会产生预防和治疗HE的新型“下游”神经药理学方法。
