Effects of low ethanol consumption on nonalcoholic steatohepatitis in mice
Effects of low ethanol consumption on nonalcoholic steatohepatitis in mice
复制标题
DOI：
10.1016/j.alcohol.2020.04.004
复制
发表时间：
2020-09-01
期刊：
影响因子：
2.3
通讯作者：
Fukusato, Toshio
中科院分区：
文献类型：
--
作者：
Takahashi, Yoshihisa;Watabe, Shiori;Fukusato, Toshio
最近的几项临床和流行病学研究表明，轻度至中度饮酒对非酒精性脂肪性肝病（NAFLD）/非酒精性脂肪性肝炎（NASH）具有抑制作用;然而，这些作用尚未在实验研究中得到证实。因此，在这项研究中，我们研究了少量乙醇消耗对NASH小鼠模型的影响。将9周龄雄性肥胖小鼠（db/db小鼠）分成以下组：对照组、高脂肪组和低乙醇组。对照组自由进食对照流质饮食，高脂肪组进食高脂肪流质饮食，低乙醇组进食补充有0.1%（w/w）乙醇的高脂肪流质饮食。8周后，处死小鼠，进行血清生化、组织病理学和分子分析。低乙醇组的血清天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平显著低于高脂肪组（分别为p = 0.033和0.037）。肝脏组织病理学分析显示，低乙醇组的小叶内和门静脉炎症明显轻于高脂肪组（分别为p = 0.018和0.041）。然而，各组之间的血清胰岛素和脂联素水平、肝脏4羟基壬烯醛（氧化损伤标志物）水平以及肝脏细胞因子和受体基因表达水平没有观察到显着差异。总之，在NASH模型小鼠中，给予少量乙醇后，血清转氨酶水平和肝脏炎症得到改善。这项研究直接证明了少量乙醇对小鼠NASH的抑制作用。这些抑制作用的机制仍有待阐明。(C)2020爱思唯尔公司All rights reserved.
Several recent clinical and epidemiological studies have suggested inhibitory effects of light-to-moderate alcohol consumption on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); however, these effects have not been confirmed in experimental studies. Therefore, in this study, we examined the effects of small amounts of ethanol consumption on a mouse model of NASH. Nine -weekold male obese mice (db/db mice) were divided into the following groups: control, high-fat, and low ethanol groups. The control group was provided ad libitum access to a control liquid diet, the high-fat group was provided access to a high-fat liquid diet, and the low-ethanol group was provided access to the high-fat liquid diet supplemented with 0.1% (w/w) ethanol. Eight weeks later, the mice were sacrificed and serum biochemical, histopathological, and molecular analyses were performed. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly lower in the low-ethanol group than in the high-fat group (p = 0.033 and 0.037, respectively). Liver histopathological analysis showed that intralobular and portal inflammation was significantly milder in the low ethanol group than in the high-fat group (p = 0.018 and 0.041, respectively). However, no significant differences were observed among the groups in serum insulin and adiponectin levels, hepatic 4hydroxynonenal (oxidative injury marker) levels, and hepatic cytokine and receptor gene expression levels. In conclusion, the serum transaminase levels and hepatic inflammation in NASH model mice improved after administration of small amounts of ethanol. This study directly demonstrated inhibitory effects of small amounts of ethanol on NASH in mice. The mechanisms underlying these inhibitory effects remain to be elucidated. (C) 2020 Elsevier Inc. All rights reserved.