Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Wenzhou 325000, Zhejiang, China.
State Key Laboratory of Infectious Diseases, Medicine School of Zhejiang University, Hangzhou 310003,China.
Cell Immunol. 2018 Jun;328:24-32. doi: 10.1016/j.cellimm.2018.03.003. Epub 2018 Mar 22.
Autoimmune hepatitis (AIH) is chronic autoimmune liver disease accompanied with the imbalance of Treg/Th17 and increased intestinal permeability. We investigated the effects of a high fiber diet and sodium butyrate on the Treg/Th17 and intestinal barrier function in an experimental autoimmune hepatitis. Intraperitoneal injection of hepatic antigen (S100) was used to induce experimental autoimmune hepatitis mice model and mice were divided into normal control, S100 model control, S100 plus high fiber diet and S100 plus sodium butyrate. Serum aminotransferases and liver histology were examined. Short chain fatty acids in feces were determined by HPLC. The ratio of CD4 + C25 + Foxp3+ Treg and CD4 + IL-17 + Th17 were evaluated by flow cytometry. Tight junction proteins Zonula ocluden, Occludin and Claudin-1 were used to assess intestinal barrier function, so does Escherichia coli protein in the liver. Mice fed with either high fiber diet or sodium butyrate showed significantly lower levers of serum aminotransferases and minor liver injury compared to that of model control. Moreover, the ratio of Treg/Th17 was significantly higher in high fiber diet and sodium butyrate fed mice than that in model control. Furthermore, high fiber diet and sodium butyrate significantly increased intestinal tight junction proteins and decreased Escherichia Coli protein in the liver. In conclusion, high fiber diet and sodium butyrate can attenuate development of autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier function.
自身免疫性肝炎(AIH)是一种慢性自身免疫性肝病,伴有 Treg/Th17 失衡和肠道通透性增加。我们研究了高纤维饮食和丁酸钠对实验性自身免疫性肝炎中 Treg/Th17 和肠道屏障功能的影响。通过腹腔注射肝抗原(S100)诱导实验性自身免疫性肝炎小鼠模型,将小鼠分为正常对照组、S100 模型对照组、S100 加高纤维饮食组和 S100 加丁酸钠组。检测血清转氨酶和肝组织学变化。采用高效液相色谱法测定粪便中短链脂肪酸。采用流式细胞术检测 CD4+ C25+ Foxp3+ Treg 和 CD4+ IL-17+ Th17 的比值。用紧密连接蛋白 Zonula ocluden、Occludin 和 Claudin-1 评估肠道屏障功能,用肝内大肠杆菌蛋白评估肠道屏障功能。与模型对照组相比,给予高纤维饮食或丁酸钠的小鼠血清转氨酶水平明显降低,肝损伤较小。此外,高纤维饮食和丁酸钠组小鼠 Treg/Th17 的比值明显高于模型对照组。此外,高纤维饮食和丁酸钠显著增加了肠道紧密连接蛋白,减少了肝内大肠杆菌蛋白。总之,高纤维饮食和丁酸钠通过调节免疫调节细胞和肠道屏障功能,可减轻自身免疫性肝炎的发展。