Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.
Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.
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DOI：
10.1111/jgh.13731
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发表时间：
2017-09
影响因子：
4.1
通讯作者：
Nagy LE
中科院分区：
文献类型：
--
作者：
Cresci GA;Glueck B;McMullen MR;Xin W;Allende D;Nagy LE
肠-肝轴受损是导致酒精性肝病的潜在因素。乙醇消耗肠道完整性，导致肠道生态失调。丁酸盐是肠道微生物群的发酵副产物，在慢性乙醇暴露后发生负面变化。本研究的目的是确定是否预防性三丁酸甘油酯可以保护肠道屏障和肝脏在联合慢性酒精中毒。暴露于5%v/v含乙醇饮食10天的C57 BL/6 J小鼠在安乐死前9小时接受单次乙醇管饲（5g/kg）。对照小鼠等热量成对喂食麦芽糖糊精乙醇。饮食中补充（5 mM）三丁酸甘油酯或甘油。对肠道和肝脏疾病活动进行组织学评估。检测细胞紧密连接蛋白（TJ）、TLRs和TNFα的蛋白和mRNA表达。使用有/没有乙醇暴露和/或丁酸钠的Caco-2单层来测试丁酸盐对肠道完整性的直接影响。慢性酗酒乙醇喂养损害肠道TJ蛋白共定位染色，然而，三丁酸甘油酯共同治疗减轻了这些影响。乙醇耗尽TJ和跨上皮电阻在Caco-2单层，但丁酸盐共治疗减少了这些影响。乙醇可诱导肝脏TLR mRNA表达和TNFα蛋白表达;然而，与三丁酸甘油酯共处理的小鼠的反应显著减弱。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：白细胞和凋亡肝细胞主要定位在仅乙醇处理的小鼠的门静脉周围，而定位在乙醇-三丁酸甘油酯小鼠的中央静脉周围占主导地位。预防性补充三丁酸甘油酯减轻了慢性酒精暴露对肠道TJ定位和肠道通透性以及肝损伤的破坏作用。
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. C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5g/kg) 9 hrs prior to euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction proteins (TJ), TLRs and TNFα were assessed. Caco-2 monolayers with/without ethanol exposure and/or sodium butyrate were used to test butyrate’s direct effects on intestinal integrity. 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 TLR mRNA expression and TNFα 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. Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury.
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影响因子：
29.4
作者：
Chen P;Torralba M;Tan J;Embree M;Zengler K;Stärkel P;van Pijkeren JP;DePew J;Loomba R;Ho SB;Bajaj JS;Mutlu EA;Keshavarzian A;Tsukamoto H;Nelson KE;Fouts DE;Schnabl B
通讯作者：
Schnabl B
影响因子：
3.2
作者：
Antonio Lopez-Moreno, Jose;Marcos, Miguel;Gine, Elena
通讯作者：
Gine, Elena
影响因子：
7.3
作者：
Ang Z;Ding JL
通讯作者：
Ding JL
影响因子：
4.7
作者：
de Conti, Aline;Tryndyak, Volodymyr;Pogribny, Igor P.
通讯作者：
Pogribny, Igor P.
DOI：
10.1177/0148607113486809
发表时间：
2013-11
期刊：
JPEN. Journal of parenteral and enteral nutrition
影响因子：
--
作者：
Cresci G;Nagy LE;Ganapathy V
通讯作者：
Ganapathy V