Zhong Wei, Li Qiong, Sun Qian, Zhang Wenliang, Zhang Jiayang, Sun Xinguo, Yin Xinmin, Zhang Xiang, Zhou Zhanxiang
Center for Translational Biomedical Research and.
Center for Translational Biomedical Research and Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC; and.
J Nutr. 2015 Dec;145(12):2690-8. doi: 10.3945/jn.115.216093. Epub 2015 Oct 14.
Zinc deficiency has been well documented in alcoholic liver disease.
This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia.
Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00-5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis.
The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group.
The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats.
锌缺乏在酒精性肝病中已有充分记载。
本研究旨在确定膳食补充锌是否对治疗酒精诱导的肠道渗漏和内毒素血症具有有益作用。
将雄性Sprague Dawley大鼠分为3组，用Lieber-DeCarli液体饲料配对喂养（PF）8周：1）对照组（PF）；2）酒精喂养组（AF；5.00 - 5.42%重量/体积乙醇）；3）补充锌的酒精喂养组（AF/Zn），添加七水硫酸锌220 ppm。PF组和AF/Zn组与AF组配对喂养。通过免疫荧光和定量聚合酶链反应（qPCR）测定肝脏炎症和内毒素信号传导。通过qPCR和蛋白质印迹分析评估肠道紧密连接和醛脱氢酶的变化。
与PF大鼠相比，AF大鼠肝脏中的巨噬细胞活化和细胞因子产生更多（P < 0.05），而AF/Zn大鼠无显著差异（P > 0.05）。AF大鼠的血浆内毒素浓度比PF大鼠高136%，而AF/Zn大鼠与PF大鼠无差异。AF大鼠的回肠通透性比PF大鼠高255%，AF/Zn大鼠比PF大鼠高19%。AF组的肠道闭合蛋白-1、闭合蛋白和紧密连接蛋白-1（ZO-1）表达降低，与PF组相比，AF/Zn组的闭合蛋白-1和ZO-1表达上调（P < 0.05）。与AF大鼠相比，AF/Zn大鼠的肠道上皮醛脱氢酶表达和活性升高（P < 0.05）。此外，与PF组相比，AF/Zn组中AF组受损的肝细胞核因子4α的回肠表达和功能显著升高。
结果表明，通过维持肠道屏障减弱肝脏内毒素信号传导有助于锌对大鼠酒精性脂肪性肝炎的保护作用。
