Excessive ethanol consumption causes cellular damage, leading to fetal alcohol syndrome and alcohol liver diseases, which are frequently seen with vitamin D (VD) deficiency. A great deal of progress has been achieved in the mechanisms of ethanol-induced hepatocyte damage. However, there are limited intervention means to reduce or rescue hepatocytes damage caused by ethanol. On the basis of our preliminary limited screen process, calcitriol showed a positive effect on protecting hepatocyte viability. Therefore, the molecular basis is worth elucidating. We found that calcitriol pretreatment markedly improved the cell viability, decreased cell apoptosis and oxidative stress and alleviated the abnormal mitochondrial morphology and membrane potential of hepatocytes induced by ethanol. Notably, autophagy was significantly enhanced by calcitriol, as evident by the increasing number of autophagosomes and autolysosomes, upregulated LC3B-Ⅱ and ATG5 levels, and promotion of p62 degradation. Furthermore, calcitriol pretreatment increased the colocalization of GFP-LC3-labeled autophagosomes with mitochondria, suggesting that calcitriol effectively promoted ethanol-induced mitophagy in hepatocytes. In addition, the inhibition of autophagy attenuated the protective and preventive effect of calcitriol. Furthermore, the effect of calcitriol on autophagy was regulated by AMPK/mTOR signaling, and signaling transduction was dependent on the Vitamin D receptor (VDR). In conclusion, calcitriol ameliorates ethanol-induced hepatocyte damage by enhancing autophagy. It may offer a convenient preventive and hepatoprotective mean for people on occasional social drink.

过量饮酒会导致细胞损伤，导致胎儿酒精综合症和酒精肝疾病，而维生素D（VD）缺乏症经常见到。在乙醇诱导的肝细胞损伤的机制上已经取得了很大的进展。但是，减少或挽救乙醇引起的肝细胞损伤的干预手段有限。在我们初步的有限筛选过程的基础上，骨化三醇显示出对保护肝细胞活力的积极作用。因此，分子基础值得阐明。我们发现，骨化三醇预处理可以显着提高细胞活力，减少细胞凋亡和氧化应激，并减轻乙醇诱导的肝细胞线粒体形态和膜电位的异常。值得注意的是，骨化三醇可显着增强自噬，自噬体和自溶酶体数量的增加，LC3B-Ⅱ和ATG5的水平上调以及p62降解的促进可以证明这一点。此外，骨化三醇预处理增加了GFP-LC3标记的自噬体与线粒体的共定位，表明骨化三醇有效地促进了乙醇诱导的肝细胞线粒体。另外，自噬的抑制减弱了骨化三醇的保护和预防作用。此外，骨化三醇对自噬的作用由AMPK / mTOR信号传导调节，信号传导依赖于维生素D受体（VDR）。总之，骨化三醇通过增强自噬来改善乙醇诱导的肝细胞损伤。它可能为偶尔社交喝酒的人提供方便的预防和保肝手段。