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酒精中毒时大脑皮质中氨基酸神经递质受体的变化:肝硬化的影响

Amino acid neurotransmitter receptor changes in cerebral cortex in alcoholism: effect of cirrhosis of the liver.

作者信息

Dodd P R, Thomas G J, Harper C G, Kril J J

机构信息

John Wilson Memorial Clinical Research Laboratory, Royal Brisbane Hospital Foundation, Sydney, Australia.

出版信息

J Neurochem. 1992 Oct;59(4):1506-15. doi: 10.1111/j.1471-4159.1992.tb08467.x.

DOI:10.1111/j.1471-4159.1992.tb08467.x
PMID:1328522
Abstract

Gamma-aminobutyric acidA/benzodiazepine receptor binding sites and the N-methyl-D-aspartate subclass of glutamate receptor sites were assessed in synaptic plasma membrane homogenates of cerebral cortex tissue obtained at autopsy from cirrhotic and noncirrhotic alcoholic patients and matched control subjects. The alcoholic patients consumed an average of greater than 80 g of ethanol/day, the control subjects less than 20 g/day. Postmortem delays up to approximately 100 h caused no significant loss of any of the binding sites; the patient and subject groups were closely matched for age. The affinities (KD) of the receptor sites did not differ between the patient and subject groups, nor between cortical regions. Using three different radioligands ([3H]muscimol, [3H]flunitrazepam, and [3H]diazepam), the gamma-aminobutyric acidA/benzodiazepine receptor complex was found to have greater density (Bmax) in superior frontal gyrus in alcoholic patients (which selectively shows morphological change in alcoholic patients), but was unchanged in motor cortex. Alcoholic patients with cirrhosis had much less pronounced changes. The density of the N-methyl-D-aspartate subclass of glutamate receptors, assessed with [3H]MK-801, did not vary across patient and subject groups.

摘要

在对死于肝硬化和非肝硬化的酗酒患者以及相匹配的对照受试者进行尸检时获取大脑皮质组织的突触质膜匀浆,对γ-氨基丁酸A/苯二氮䓬受体结合位点以及谷氨酸受体位点的N-甲基-D-天冬氨酸亚类进行了评估。酗酒患者平均每天摄入乙醇超过80克,对照受试者每天摄入少于20克。长达约100小时的死后延迟并未导致任何结合位点显著丧失;患者组和受试者组在年龄上紧密匹配。患者组和受试者组之间以及不同皮质区域之间,受体位点的亲和力(KD)并无差异。使用三种不同的放射性配体([3H]蝇蕈醇、[3H]氟硝西泮和[3H]地西泮),发现酗酒患者(其额叶上回选择性地呈现出形态学变化)额叶上回中的γ-氨基丁酸A/苯二氮䓬受体复合物具有更高的密度(Bmax),但运动皮质中的该复合物密度未发生变化。患有肝硬化的酗酒患者的变化则不太明显。用[3H]MK-801评估的谷氨酸受体N-甲基-D-天冬氨酸亚类的密度在患者组和受试者组之间并无差异。

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