Diurnal variations in intestinal barrier integrity and liver pathology in mice: implications for alcohol binge.
Diurnal variations in intestinal barrier integrity and liver pathology in mice: implications for alcohol binge.
复制标题
小鼠肠道屏障完整性和肝脏病理学的昼夜变化：对酗酒的影响。
DOI：
10.1152/ajpgi.00103.2017
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Keshavarzian,Ali
中科院分区：
文献类型：
--
作者：
Voigt,RobinM;Forsyth,ChristopherB;Shaikh,Maliha;Zhang,Lijuan;Raeisi,Shohreh;Aloman,Costica;Preite,NailliwZ;DonohueJr,TerrenceM;Fogg,Louis;Keshavarzian,Ali
最近的研究表明，昼夜节律调节肠道屏障的完整性，但尚不清楚屏障完整性是否存在每日变化。本研究调查了肠屏障完整性的日常变化，包括在一天中的不同时间饮酒后酒精诱导的肠屏障功能障碍是否存在差异，以及这是否与并发肝损伤有关。C57BL6/J雄性小鼠分别饲喂标准鼠粮、含酒精液体饮食或酒精控制饮食4周。Duringweek 5(即。（第43-45天），小鼠在每天同一时间三次灌胃酒精（6 g/kg）或对照组（磷酸盐缓冲盐水）。第二天暴食后立即评估肠通透性。在第三次也是最后一次狂欢四小时后，老鼠被安乐死，并收集组织样本。结果证明了时间、酒精和/或酒精相互作用的时间对饮食和结果的特异性影响。具体来说，酗酒会强烈影响肠道屏障完整性的标志物，而肝脏标志物则会受到一天中时间的强烈影响。只有肠道通透性（即三氯蔗糖）受时间影响显著，同时也表现出时间与狂欢的相互作用，提示狂欢的时间影响结肠通透性。这项研究调查了肠屏障完整性的日常变化，包括在一天中的不同时间饮酒后酒精诱导的肠屏障功能障碍是否存在差异，以及这是否与并发肝损伤有关。我们得出结论：1)酗酒显著影响肠道通透性指标，2)一天中的时间显著影响肝脏预后，3)一天中的时间影响结肠通透性。
Recent studies suggest that circadian rhythms regulate intestinal barrier integrity, but it is not clear whether there are daily variations in barrier integrity. This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. C57BL6/J male mice were fed a standard chow diet, an alcohol-containing liquid diet, or an alcohol control diet for 4 wk. Duringweek 5(i.e., ondays 43–45), mice received three once-daily gavages of alcohol (6 g/kg) or the control (phosphate-buffered saline) at the same time each day. Immediately after the binge on the second day, intestinal permeability was assessed. Four hours after the third and final binge, mice were euthanized and tissue samples collected. The results demonstrated diet-specific and outcome-specific effects of time, alcohol, and/or time by alcohol interaction. Specifically, the alcohol binge robustly influenced markers of intestinal barrier integrity, and liver markers were robustly influenced by time of day. Only intestinal permeability (i.e., sucralose) demonstrated a significant effect of time and also showed a binge by time interaction, suggesting that the time of the alcohol binge influences colonic permeability.NEW & NOTEWORTHYThis study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. We conclude that1) alcohol binge significantly impacted markers of intestinal permeability,2) time of day significantly affected liver outcomes, and3) the time of day influenced colonic permeability.