This study aimed to develop a well-characterized mouse model of alcoholic hepatitis (AH) regression. Male C57BL/6J mice were fed a Lieber-DeCarli (LD) control diet or LD containing 5% ethanol for ten days followed by one binge, which is the chronic-binge model of AH developed by the National Institute on Alcohol Abuse and Alcoholism. To determine AH regression, mice previously exposed to ethanol were put on LD control diet and metabolic and inflammatory features were monitored weekly for three weeks. Serum alcohol, total cholesterol, and alanine transaminase levels were increased in ethanol-fed mice, which declined to those of no ethanol controls within one and three weeks after ethanol withdrawal, respectively. Serum malondialdehyde was increased with ethanol feeding, but it was restored to no ethanol control levels within one week. Ethanol-induced changes in the hepatic expression of genes involved in lipogenesis, fatty acid oxidation, ethanol metabolism, and antioxidant response were restored to those of no ethanol controls after 3 weeks of ethanol withdrawal. Also, ethanol-induced hepatic inflammation was gradually decreased during the 3 weeks of ethanol withdrawal. Hepatic nicotinamide adenine dinucleotide (NAD⁺) levels and the expression of enzymes involved in the NAD⁺ salvage pathway were decreased by ethanol feeding, which was mitigated after ethanol withdrawal. Ethanol significantly lowered hepatic sirtuin 1 expression, but its levels were restored with ethanol cessation. This study established a mouse model of AH regression, which can be used as a preclinical model to study the potential of dietary bioactives or therapeutic agents on AH regression.

本研究旨在开发一种特征良好的酒精性肝炎 (AH) 回归小鼠模型。给雄性 C57BL/6J 小鼠喂食 Lieber-DeCarli (LD) 对照饮食或含有 5% 乙醇的 LD，持续 10 天，然后进行一次暴饮暴食，这是由国家酒精滥用和酒精中毒研究所开发的 AH 慢性暴食模型。为了确定 AH 回归，将先前暴露于乙醇的小鼠置于 LD 对照饮食中，并每周监测代谢和炎症特征，持续三周。乙醇喂养小鼠的血清酒精、总胆固醇和丙氨酸转氨酶水平升高，分别在乙醇戒断后 1 周和 3 周内降至无乙醇对照组。血清丙二醛随着乙醇喂养而增加，但在一周内恢复到无乙醇控制水平。在乙醇戒断 3 周后，乙醇诱导的与脂肪生成、脂肪酸氧化、乙醇代谢和抗氧化反应相关的基因的肝脏表达变化恢复到无乙醇对照组的水平。此外，乙醇引起的肝脏炎症在 3 周的乙醇戒断期间逐渐减少。肝烟酰胺腺嘌呤二核苷酸（NAD⁺ ) 水平和参与 NAD ⁺补救途径的酶的表达因乙醇喂养而降低，在乙醇戒断后得到缓解。乙醇显着降低肝脏sirtuin 1的表达，但其水平随着乙醇的停止而恢复。本研究建立了 AH 回归的小鼠模型，可作为临床前模型研究膳食生物活性物质或治疗剂对 AH 回归的潜力。