Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy.
Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy.
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人和动物肝性脑病中的内源性苯二氮卓受体配体。
DOI：
10.1111/j.1471-4159.1990.tb05790.x
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发表时间：
1990
影响因子：
4.7
通讯作者：
Costa,E
中科院分区：
文献类型：
--
作者：
Olasmaa,M;Rothstein,JD;Guidotti,A;Weber,RJ;Paul,SM;Spector,S;Zeneroli,ML;Baraldi,M;Costa,E
在人类和大鼠肝性脑病模型中研究了内源性苯二氮卓受体配体在肝性脑病发病机制中的作用。通过酸处理和 HPLC 纯化，从大鼠脑和人脑脊液中提取内源性苯二氮卓配体。使用放射受体结合测定和抗苯二氮卓抗体放射免疫测定对这些内源性苯二氮卓配体进行检测和部分表征。根据洗脱曲线和抗苯二氮卓抗体反应性，在人和大鼠组织中鉴定出四种不同的苯二氮卓受体配体，其中两种可能是地西泮和去甲基地西泮。肝性脑病患者的人脑脊液和血清中内源性苯二氮卓受体配体的含量比对照或患有肝病的非脑病患者的脑脊液多约 10 倍。在患有暴发性肝衰竭的大鼠中，脑内苯二氮卓受体配体化合物的水平也增加了约10倍，但在患有门静脉分流术（慢性肝病模型）的大鼠中则没有增加。这些物质浓度的增加可能对行为产生重要影响，并可能导致肝性脑病的发病机制。
The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti‐benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti‐benzodiazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained ∼ 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased ∼ 10‐fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.