预防性三丁酸甘油酯治疗可减轻慢性暴饮乙醇诱导的肠道屏障和肝损伤。
Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.
作者信息
Cresci Gail A, Glueck Bryan, McMullen Megan R, Xin Wei, Allende Daniella, Nagy Laura E
机构信息
Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
出版信息
J Gastroenterol Hepatol. 2017 Sep;32(9):1587-1597. doi: 10.1111/jgh.13731.
BACKGROUND AND AIM
Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure.
METHODS
C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll-like receptors, and tumor necrosis factor-alpha were assessed. Caco-2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity.
RESULTS
Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic toll-like receptor mRNA expression and tumor necrosis factor-alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice.
CONCLUSIONS
Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury.
背景与目的
肠-肝轴受损是导致酒精性肝病的一个潜在因素。乙醇会破坏肠道完整性并导致肠道菌群失调。丁酸盐是肠道微生物群的发酵副产物，长期乙醇暴露后其水平会呈负向改变。本研究旨在确定预防性补充三丁酸甘油酯是否能在慢性-暴饮联合乙醇暴露期间保护小鼠的肠道屏障和肝脏。
方法
C57BL/6J小鼠食用含5%（体积/体积）乙醇的饲料10天，在安乐死9小时前接受一次乙醇灌胃（5克/千克）。对照小鼠以等热量方式配对喂食麦芽糖糊精以替代乙醇。饲料中补充（5毫摩尔）三丁酸甘油酯或甘油。通过组织学评估肠道和肝脏疾病活动。评估紧密连接（TJ）蛋白、Toll样受体和肿瘤坏死因子-α的蛋白质和mRNA表达。使用暴露或未暴露于乙醇和/或丁酸钠的Caco-2单层细胞来测试丁酸盐对肠道完整性的直接影响。
结果
慢性-暴饮乙醇喂养损害了肠道TJ蛋白共定位染色；然而，三丁酸甘油酯联合治疗减轻了这些影响。乙醇降低了Caco-2单层细胞中的TJ和跨上皮电阻，但丁酸盐联合治疗减轻了这些影响。乙醇诱导肝脏Toll样受体mRNA表达和肿瘤坏死因子-α蛋白表达；然而，在三丁酸甘油酯联合治疗的小鼠中，这种反应明显减弱。三丁酸甘油酯改变了中性粒细胞和单个肝细胞死亡的定位：仅接受乙醇治疗的小鼠中，白细胞和凋亡肝细胞主要定位于门静脉周围，而在乙醇-三丁酸甘油酯联合治疗的小鼠中，定位主要集中在中央静脉周围。
结论
预防性补充三丁酸甘油酯减轻了慢性-暴饮联合乙醇暴露对肠道TJ定位破坏、肠道通透性和肝脏损伤的影响。
Zotero 插件