STUDIES OF RELATING TO THE PATHOGENESIS OF HEPATIC ENCEPHALOPATHY

家兔视觉诱发反应（VERs）的异常模式 暴发性肝衰竭导致肝性脑病（HE） (FHF)类似于由一种 巴比妥酸盐、苯并二氮杂卓（BZ）或γ-氨基丁酸盐 酸（GABA）激动剂。 由于这些药物通过以下方式诱导神经抑制： 增强GABA能抑制性神经传递， 结果，他们的相互作用与特定的结合位点上的 突触后神经膜上的GABA/BZ受体复合物， 这些发现提示HE中神经元活动的模式 可能类似于与GABA激活相关的 抑制性神经递质系统 考虑到快速的 GABA的代谢，一种改良的Oldendorf技术， 使用血管标记物，已经用于 证明血浆GABA的脑摄取指数是 在兔HE模型中增加。 两个方面的改进（ 临床和电生理（VER波形））诱导， GABA受体拮抗剂BZ受体 拮抗剂和氯离子通道阻滞剂，并在大鼠与FHF， BZ受体拮抗剂和BZ的部分反向激动剂 受体的 家兔浦肯野神经元的自发活动 在HE表现出增加的敏感性抑郁症的GABA 激动剂和BZ激动剂，但由BZ受体兴奋 对手。 这些结果表明，在FHF所致HE中：（i） GABA能张力增加，这既不是种属， 模型依赖性;（ii）阻断GABA或BZ受体 改善HE;（iii）BZ受体拮抗剂可能具有临床意义 在治疗HE中的价值;和（iv）内源性BZ受体激动剂 可以为他做贡献。

The abnormal pattern of visual evoked responses (VERs) in rabbits with hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF) resembles that associated with coma induced by a barbiturate, a benzodiazepine (BZ) or a gamma-amino-butyric acid (GABA) agonist. As these drugs induce neural inhibition by potentiating GABAergic inhibitory neurotransmission as a consequence of their interaction with specific binding sites on the GABA/BZ receptor complex on postsynaptic neural membranes, these findings suggest that the pattern of neuronal activity in HE may resemble that associated with activation of the GABA inhibitory neurotransmitter system. To take account of the rapid metabolism of GABA, a modified Oldendorf technique, which employed the use of a vascular marker, has been used to demonstrate that the brain uptake index of plasma GABA is increased in the rabbit model of HE. Ameliorations of HE (both clinical and electrophysiologic (VER waveform)) were induced in rabbits with FHF by a GABA receptor antagonist, a BZ receptor antagonist and a chloride channel blocker and in rats with FHF by a BZ receptor antagonist and a partial inverse agonist of the BZ receptor. The spontaneous activity of Purkinje neurons of rabbits in HE exhibited increased sensitivity to depression by a GABA agonist and a BZ agonist, but was excited by BZ receptor antagonists. These findings suggest that in HE due to FHF: (i) There is increased GABAergic tone which is neither species nor model dependent; (ii) Blockading GABA or BZ receptors ameliorates HE; (iii) BZ receptor antagonists may be of clinical value in treating HE; and (iv) An endogenous BZ receptor agonist may contribute to HE.