Mullen K D, Martin J V, Mendelson W B, Kaminsky-Russ K, Jones E A
Department of Medicine, Cleveland Metropolitan General Hospital, Case Western Reserve University, Ohio 44109.
Metab Brain Dis. 1989 Dec;4(4):253-60. doi: 10.1007/BF00999771.
Based on the reversal of hepatic encephalopathy in animal models with administration of specific benzodiazepine receptor antagonists, it has been postulated that this syndrome may be mediated by an endogenous benzodiazepine-like compound. In this study using a radio-receptor assay, evidence for the existence of this substance has been demonstrated in cerebrospinal fluid but not sera of rabbits with hepatic encephalopathy due to galactosamine-induced hepature failure. Cerebrospinal fluid from rabbits with hepatic encephalopathy caused 36.1 +/- 5.03% displacement of 3H-Ro 15-1788 specific binding to cortical benzodiazepine receptors, compared to 11.7 +/- 0.76% in control animals (P less than 0.01). The benzodiazepine receptor binding activity has been shown to behave as a competitive inhibitor of radiolabeled benzodiazepine receptor binding. The finding of endogenous benzodiazepine binding activity affords a potential explanation for the amelioration of hepatic encephalopathy in this model with the administration of benzodiazepine receptor antagonists.
基于在动物模型中给予特定苯二氮䓬受体拮抗剂后肝性脑病得到逆转，有人推测该综合征可能由内源性苯二氮䓬样化合物介导。在这项使用放射受体测定法的研究中，已在脑脊液中证实了这种物质的存在，但在因半乳糖胺诱导的肝衰竭而患有肝性脑病的兔子血清中未发现。患有肝性脑病的兔子的脑脊液导致3H-Ro 15-1788与皮质苯二氮䓬受体的特异性结合发生36.1±5.03%的位移，而对照动物为11.7±0.76%（P<0.01）。苯二氮䓬受体结合活性已被证明表现为放射性标记的苯二氮䓬受体结合的竞争性抑制剂。内源性苯二氮䓬结合活性的发现为在该模型中给予苯二氮䓬受体拮抗剂后肝性脑病得到改善提供了一种潜在的解释。
