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小鼠酒精代谢快速增加(SIAM):四种近交系小鼠短期乙醇处理对乙醇消除作用的比较

Swift increase in alcohol metabolism (SIAM) in the mouse: comparison of the effect of short-term ethanol treatment on ethanol elimination in four inbred strains.

作者信息

Thurman R G, Paschal D, Abu-Murad C, Pekkanen L, Bradford B U, Bullock K, Glassman E

出版信息

J Pharmacol Exp Ther. 1982 Oct;223(1):45-9.

PMID:7120126
Abstract

Ethanol metabolism increases 2 to 3 hr after the administration of ethanol. This phenomenon, called the swift increase in alcohol metabolism, has been compared in four inbred strains of mice (DBA/2J, C3H/HeJ, AKR/J and C57BL/6J). Basal rates of ethanol elimination were determined in individual mice after an i.p. injection of ethanol (2 g/kg). Little variability in this basal rate of ethanol elimination was observed within each strain. Mice were then exposed to ethanol vapor (20--22 mg/l) and rates of ethanol elimination were determined every 2 hr for 8 hr. By 2 to 3 hr, the rates of ethanol elimination initially increased 2- to 3-fold and then declined toward basal rates over the 8-hr interval in all strains studied. In another experiment, the dose of ethanol was varied to produce blood ethanol levels ranging from 50 to 250 mg/100 ml in both basal- and ethanol vapor-treated mice. Ethanol elimination increased greater than 1.5-fold in all four strains studied when basal rates were compared to rates observed after 4 hr of vapor treatment at the same blood ethanol level; however, the dose at which the maximal increase occurred differed among the strains. DBA/2J mice exhibited a maximal increase in the rate of ethanol elimination when ethanol concentrations were in the range of 30 to 50 mg/100 ml; the increase was smaller as the dose was increased. In contrast, AKR/J and C57BL/6J mice required 100 to 150 mg/100 ml of ethanol to activate the swift increase in alcohol metabolism effect. These data indicate clearly that the swift increase in alcohol metabolism effect is a common phenomenon and that dose and time relations differ in various inbred strains of mice.

摘要

乙醇给药后2至3小时,乙醇代谢增加。这种现象称为酒精代谢迅速增加,已在四种近交系小鼠(DBA/2J、C3H/HeJ、AKR/J和C57BL/6J)中进行了比较。腹腔注射乙醇(2 g/kg)后,测定各小鼠的乙醇基础消除率。各品系内乙醇基础消除率的变异性很小。然后让小鼠暴露于乙醇蒸气(20 - 22 mg/l)中,并在8小时内每2小时测定一次乙醇消除率。到2至3小时时,所有研究品系的乙醇消除率最初增加2至3倍,然后在8小时内降至基础水平。在另一项实验中,改变乙醇剂量以使基础处理和乙醇蒸气处理小鼠的血液乙醇水平在50至250 mg/100 ml范围内。当将基础水平与在相同血液乙醇水平下进行4小时蒸气处理后观察到的速率进行比较时,所有四个研究品系的乙醇消除率均增加超过1.5倍;然而,最大增加发生时的剂量在各品系间有所不同。当乙醇浓度在30至50 mg/100 ml范围内时,DBA/2J小鼠的乙醇消除率出现最大增加;随着剂量增加,增加幅度变小。相比之下,AKR/J和C57BL/6J小鼠需要100至150 mg/100 ml的乙醇来激活酒精代谢迅速增加效应。这些数据清楚地表明,酒精代谢迅速增加效应是一种常见现象,并且在不同近交系小鼠中剂量和时间关系有所不同。

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