Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina, United States of America.
PLoS One. 2013 Oct 14;8(10):e76522. doi: 10.1371/journal.pone.0076522. eCollection 2013.
Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency.
临床研究表明，与健康对照组相比，酗酒者的膳食锌摄入量较低。本研究旨在确定膳食锌缺乏与乙醇摄入在酒精性肝病发病机制中的相互作用。C57BL/6N 小鼠接受 8 周的 4 种实验性液体饮食喂养：（1）锌充足饮食，（2）锌充足饮食加乙醇，（3）锌缺乏饮食，和（4）锌缺乏饮食加乙醇。乙醇暴露与充足的膳食锌导致肝脏损伤，表现为血浆丙氨酸氨基转移酶水平升高、肝脂质蓄积增加和炎症细胞浸润增加。单独的膳食锌缺乏增加肝脂质含量，但不引起肝炎症。膳食锌缺乏对乙醇诱导的肝损伤具有协同作用。膳食锌缺乏加剧了乙醇对与脂质代谢和炎症反应相关的肝基因的影响。膳食锌缺乏加重了乙醇诱导的肝内促氧化剂和抗氧化酶之间的失衡以及细胞死亡受体在肝内的表达。膳食锌缺乏加剧了乙醇诱导的血浆瘦素减少，尽管它不影响乙醇诱导的白色脂肪组织质量减少。膳食锌缺乏还加重了乙醇诱导的肠道通透性增加和血浆内毒素升高。这些结果首次表明，膳食锌缺乏是酒精性肝病的一个危险因素，多个肝内和肝外因素可能介导锌缺乏的有害作用。
