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慢性给予乙醇后小鼠肝脏中与乙醇代谢相关的酶活性变化。

Changes in hepatic enzyme activities related to ethanol metabolism in mice following chronic ethanol administration.

作者信息

Kishimoto R, Fujiwara I, Kitayama S, Goda K, Nakata Y

机构信息

Faculty of Nutrition, Kobe Gakuin University, Japan.

出版信息

J Nutr Sci Vitaminol (Tokyo). 1995 Oct;41(5):527-43. doi: 10.3177/jnsv.41.527.

DOI:10.3177/jnsv.41.527
PMID:8750204
Abstract

Male mice of three strains, C57BL, DBA and C3H/He, were fed on commercial food with 10% (v/v) ethanol solution as drinking liquid ad libitum for eighty days, and the changes in the activities of enzymes in the metabolic pathway of ethanol in the liver were examined. C57BL and C3H/He mice showed a preference for drinking the 10% (v/v) ethanol solution, while DBA mice did not. The ethanol intake g/g of body weight of C3H/He mice showed the highest value among all three strains and that of C57BL mice tended to show higher value than that of DBA mice. The liver weights of C57BL and C3H/He mice increased significantly following chronic ethanol administration, but that of DBA did not. The cytosolic enzyme alcohol dehydrogenase (ADH) showed no changes in any of the strains following chronic ethanol administration. The microsomal ethanol-oxidizing system (MEOS) of C57BL mice exhibited approximately 2-fold higher activity compared to that of DBA and C3H/He mice but did not increase in any strain following chronic ethanol administration. However, the microsomal aniline hydroxylase activity in the liver increased significantly in C57BL and C3H/He mice following chronic administration of ethanol. The microsomal cytochrome P-450 content also tended to slightly increase in the same strains of mice. It seemed that cytochrome P-450IIE1 was induced in the liver microsomes of these strains. Total aldehyde dehydrogenase (ALDH) activities together with high-Km ALDH activity increased markedly in the microsomes of C57BL mice and tended to increase in C3H/He mice, while it did not change in DBA mice following chronic ethanol administration. In the mitochondria of C57BL, total ALDH activities increased slightly and high-Km ALDH activities tended to increase. These mitochondrial ALDH activities of C3H/He and DBA mice tended to increase following chronic ethanol administration. The cytosolic ALDH activity showed no changes in any strain of mice following chronic ethanol administration. It seemed that in the microsomes, the activities of enzymes related to oxidation of ethanol increased in C57BL and C3H/He mice, which tended to consume a large amount of ethanol, and did not in DBA mice which tended to consume a small amount of it. It seemed that the increases in activities of enzymes related to oxidation of acetaldehyde in the microsomes and in the mitochondria were responsible for the strain difference.

摘要

以C57BL、DBA和C3H/He三种品系的雄性小鼠为研究对象,用含10%(体积/体积)乙醇溶液的市售食物作为饮用水,随意饮用80天,检测肝脏中乙醇代谢途径中酶活性的变化。C57BL和C3H/He小鼠表现出对饮用10%(体积/体积)乙醇溶液的偏好,而DBA小鼠则不然。在所有三个品系中,C3H/He小鼠每克体重的乙醇摄入量最高,C57BL小鼠的乙醇摄入量往往高于DBA小鼠。长期给予乙醇后,C57BL和C3H/He小鼠的肝脏重量显著增加,但DBA小鼠的肝脏重量没有增加。胞质酶乙醇脱氢酶(ADH)在长期给予乙醇后,在任何品系中均未发生变化。C57BL小鼠的微粒体乙醇氧化系统(MEOS)活性比DBA和C3H/He小鼠高约2倍,但在长期给予乙醇后,任何品系的MEOS活性均未增加。然而,长期给予乙醇后,C57BL和C3H/He小鼠肝脏中的微粒体苯胺羟化酶活性显著增加。相同品系小鼠的微粒体细胞色素P-450含量也有轻微增加的趋势。似乎这些品系的肝脏微粒体中诱导了细胞色素P-450IIE1。长期给予乙醇后,C57BL小鼠微粒体中的总醛脱氢酶(ALDH)活性和高Km ALDH活性显著增加,C3H/He小鼠有增加趋势,而DBA小鼠则无变化。在C57BL小鼠的线粒体中,总ALDH活性略有增加,高Km ALDH活性有增加趋势。长期给予乙醇后,C3H/He和DBA小鼠的这些线粒体ALDH活性有增加趋势。长期给予乙醇后,任何品系小鼠的胞质ALDH活性均无变化。似乎在微粒体中,与乙醇氧化相关的酶活性在倾向于消耗大量乙醇的C57BL和C3H/He小鼠中增加,而在倾向于消耗少量乙醇的DBA小鼠中则没有增加。似乎微粒体和线粒体中与乙醛氧化相关的酶活性增加是品系差异的原因。

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