为期5周的乙醇喂养对乙醛脱氢酶2基因敲除小鼠肝脏的影响。
Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice.
作者信息
Matsumoto Akiko, Kawamoto Toshihiro, Mutoh Fumihiro, Isse Toyohi, Oyama Tsunehiro, Kitagawa Kyoko, Nakayama Keiichi I, Ichiba Masayoshi
机构信息
Departments of Social and Environmental Medicine, Saga Medical School, Saga, Japan.
出版信息
Pharmacogenet Genomics. 2008 Oct;18(10):847-52. doi: 10.1097/FPC.0b013e328307a0a9.
OBJECTIVE
The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH22, is very common in East Asian countries, and the mutated ALDH2 protein derived from ALDH22 lacks the ability of acetaldehyde metabolization. Our aim was to determine the consequences of the ALDH2 polymorphism on ethanol-administered liver tissue.
METHODS
Aldh2+/+, +/-, and -/- mice were fed with ethanol solution and standard hard feed for 5 weeks.
RESULTS
The serum alanine aminotransferase (ALT) level in the Aldh2-/- mice clearly decreased upon ethanol feeding, in contrast to Aldh2+/+ mice, in which the ALT level was unchanged. The levels of malondialdehyde, phospho extracellular signal-regulated kinase 2, and tumor necrosis factor-alpha in the liver tissue all correlated with the ALT level.
CONCLUSION
These findings suggest that ethanol intake in the presence of inactive ALDH2 decreases the serum ALT level following a decrease in oxidative stress and tumor necrosis factor-alpha secretion.
目的
醛脱氢酶2（ALDH2）的多态性，即ALDH22，在东亚国家非常常见，由ALDH22衍生的突变型ALDH2蛋白缺乏乙醛代谢能力。我们的目的是确定ALDH2多态性对乙醇处理的肝脏组织的影响。
方法
给野生型（Aldh2+/+)、杂合子（+/−）和纯合子（−/−）小鼠喂食乙醇溶液和标准硬饲料5周。
结果
与野生型小鼠（ALT水平不变）相比，喂食乙醇后，纯合子小鼠血清丙氨酸氨基转移酶（ALT）水平明显下降。肝组织中丙二醛、磷酸化细胞外信号调节激酶2和肿瘤坏死因子-α的水平均与ALT水平相关。
结论
这些发现表明，在无活性ALDH2存在的情况下摄入乙醇，会在氧化应激和肿瘤坏死因子-α分泌减少后降低血清ALT水平。
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