Department of Pathology, School of Medicine, International University of Health and Welfare, 4-3 Kouzunomori, Narita, Chiba, 286-8686, Japan.
Department of Pathology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Alcohol. 2020 Sep;87:51-61. doi: 10.1016/j.alcohol.2020.04.004. Epub 2020 Jun 15.
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-week-old 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 4-hydroxynonenal (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.
几项最近的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）有抑制作用；然而，这些作用在实验研究中尚未得到证实。因此，在这项研究中，我们研究了少量乙醇摄入对 NASH 小鼠模型的影响。将 9 周龄雄性肥胖小鼠（db/db 小鼠）分为以下几组：对照组、高脂肪组和低乙醇组。对照组自由摄入对照液体饮食，高脂肪组自由摄入高脂肪液体饮食，低乙醇组摄入补充 0.1%（w/w）乙醇的高脂肪液体饮食。8 周后处死小鼠，进行血清生化、组织病理学和分子分析。低乙醇组血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平明显低于高脂肪组（p=0.033 和 0.037）。肝组织病理学分析显示，低乙醇组肝小叶和门脉炎症明显轻于高脂肪组（p=0.018 和 0.041）。然而，各组间血清胰岛素和脂联素水平、肝 4-羟壬烯醛（氧化损伤标志物）水平以及肝细胞因子和受体基因表达水平无显著差异。总之，少量乙醇给药后 NASH 模型小鼠的血清转氨酶水平和肝内炎症得到改善。本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。
