Tokuda Yuki, Miura Natsuko, Kobayashi Misato, Hoshinaga Yukiko, Murai Atsushi, Aoyama Hiroaki, Ito Hiroyuki, Morita Tatsuya, Horio Fumihiko
Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
Toxicology Division, Institute of Environmental Toxicology, Ibaraki, Japan.
Nutrition. 2015 Feb;31(2):373-9. doi: 10.1016/j.nut.2014.07.009. Epub 2014 Aug 1.
The aim of this study was to determine whether ascorbic acid (AsA) deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver.
The mechanisms by which AsA deficiency provokes inflammatory changes in the liver were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient (300 mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for 14 or 18 d.
On day 14, the hepatic mRNA levels of acute-phase proteins and inflammation-related genes were significantly higher in the AsA-deficient group than the control group, and these elevations by AsA deficiency were exacerbated on day 18. The serum concentrations of interleukin (IL)-1β and IL-6, which induce acute-phase proteins in the liver, were also significantly elevated on day 14 in the AsA-deficient group compared with the respective values in the control group. IL-1β mRNA levels in the liver, spleen, and lung were increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood endotoxin concentration was significantly higher in the AsA-deficient group than in the control group, and a significant correlation between serum IL-1β concentrations and portal endotoxin concentrations was found in AsA-deficient rats. In the histologic analysis of the ileum tissues, the number of goblet cells per villi was increased by AsA deficiency.
These results suggest that AsA deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver.
本研究旨在确定抗坏血酸（AsA）缺乏引起的内毒素从胃肠道流入门静脉血是否会导致肝脏的炎症变化。
在成骨障碍史氏（ODS）大鼠（无法合成AsA）中研究AsA缺乏引发肝脏炎症变化的机制。雄性ODS大鼠（6周龄）被喂食含充足（300mg/kg）AsA的饮食（对照组）或不含AsA的饮食（AsA缺乏组）14天或18天。
在第14天，AsA缺乏组中急性期蛋白和炎症相关基因的肝脏mRNA水平显著高于对照组，且AsA缺乏导致的这些升高在第18天加剧。诱导肝脏中急性期蛋白的白细胞介素（IL）-1β和IL-6的血清浓度在AsA缺乏组第14天时也显著高于对照组的相应值。AsA缺乏使肝脏、脾脏和肺中的IL-1β mRNA水平升高。此外，在第14天和第18天，AsA缺乏组的门静脉血内毒素浓度均显著高于对照组，并且在AsA缺乏的大鼠中发现血清IL-1β浓度与门静脉内毒素浓度之间存在显著相关性。在回肠组织的组织学分析中，AsA缺乏使每个绒毛的杯状细胞数量增加。
这些结果表明，AsA缺乏引起的内毒素从胃肠道流入门静脉血会导致肝脏的炎症变化。
