China Agricultural University, Beijing, China.
Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G625-33. doi: 10.1152/ajpgi.00350.2009. Epub 2010 Feb 18.
Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.
肠道屏障的破坏是酒精性内毒素血症和肝炎发展的一个因果因素。本研究旨在确定锌缺乏是否与酒精对肠道屏障的有害影响有关。将小鼠进行配对喂养，分别给予酒精或等热量的液体饮食 4 周，同时检测与血液内毒素水平升高相关的肝炎。酒精暴露显著增加了回肠的通透性，但不影响十二指肠或空肠的屏障功能。在酒精喂养的小鼠中检测到紧密连接蛋白在回肠上皮的减少，尽管酒精暴露没有引起明显的组织病理学变化。酒精暴露显著降低了回肠锌浓度，同时伴有活性氧的积累。Caco-2 细胞培养表明，由于氧化应激，酒精暴露会增加细胞内游离锌。锌剥夺导致上皮屏障破坏，同时紧密连接蛋白在 Caco-2 单层细胞中解体。此外，轻微的锌剥夺会加剧酒精对上皮屏障的有害影响。总之，远端小肠的上皮屏障功能障碍在酒精引起的肠道通透性增加中起重要作用，而氧化应激引起的锌缺乏可能通过直接作用于紧密连接蛋白或通过对酒精作用的敏感性来干扰肠道屏障功能。
