Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2012 Jan;125(2):306-11.
Nonalcoholic fatty liver disease (NAFLD) has emerged as the major cause of chronic liver injury. Intestinal barrier plays an important role in the pathogenis of NAFLD. The aim of this article was to assess intestinal immune barrier function during the development of NAFLD.
Totally 60 male Sprague-Dawley (SD) rats were divided into 2 groups: normal diet (ND) group and high-fat diet (HFD) group. NAFLD rat model was established in the HFD rat group. Portal blood endotoxin level was assessed by limulus test. The percentage of CD4+ cells and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were analysed by flow cytometry. Intestinal secretory immunoglobulin A (SIgA) level was evaluated by enzyme-linked immunosorbent assay. Paired Student's t test was used for the statistic analysis.
HFD rats presented with simple steatosis at the 4th and 8th week and progressed to nonalcoholic steatohepatitis at the 12th week. Elevated lipopolysaccharides (LPS) level in HFD rats was observed at the 8th week ((1.54 ± 0.30) times of ND group, P < 0.01). CD4/CD8 ratios in PBMC and PP of HFD rats were increased at the 4th week ((1.50 ± 0.47) and (1.63 ± 0.34) times of ND group, P < 0.05) and decreased at the 8th week ((0.50 ± 0.16) and (0.61 ± 0.26) times of ND group, P < 0.05). At the 12th week, CD4/CD8 ratio ((1.47 ± 0.46) times, P < 0.05) in PP increased to levels observed in the 4th week. Intestinal SIgA expression of HFD rats was remarkably up-regulated at 12th week ((2.70 ± 1.65) times, P < 0.05).
Liver-gut axis in rats with NAFLD may mediate and improve intestinal immune function by increased CD4/CD8 ratio in PP and increased production of SIgA.
非酒精性脂肪性肝病（NAFLD）已成为慢性肝损伤的主要原因。肠道屏障在 NAFLD 的发病机制中起着重要作用。本文旨在评估 NAFLD 发展过程中的肠道免疫屏障功能。
雄性 Sprague-Dawley（SD）大鼠 60 只，随机分为正常饮食（ND）组和高脂饮食（HFD）组。HFD 组大鼠建立 NAFLD 大鼠模型。通过鲎试验评估门静脉血内毒素水平。采用流式细胞术分析外周血单个核细胞（PBMC）和派尔集合淋巴结（PP）中 CD4+细胞和 CD8+细胞的百分比。采用酶联免疫吸附试验（ELISA）评估肠道分泌型免疫球蛋白 A（SIgA）水平。采用配对学生 t 检验进行统计学分析。
HFD 组大鼠在第 4 周和第 8 周出现单纯性脂肪变性，并在第 12 周进展为非酒精性脂肪性肝炎。HFD 组大鼠在第 8 周时观察到脂多糖（LPS）水平升高（是 ND 组的 1.54±0.30 倍，P<0.01）。HFD 组大鼠 PBMC 和 PP 中的 CD4/CD8 比值在第 4 周升高（是 ND 组的 1.50±0.47 倍和 1.63±0.34 倍，P<0.05），在第 8 周下降（是 ND 组的 0.50±0.16 倍和 0.61±0.26 倍，P<0.05）。在第 12 周，PP 中的 CD4/CD8 比值（是第 4 周的 1.47±0.46 倍，P<0.05）升高至第 4 周的水平。HFD 组大鼠肠道 SIgA 表达在第 12 周显著上调（是 ND 组的 2.70±1.65 倍，P<0.05）。
NAFLD 大鼠的肝肠轴可能通过增加 PP 中的 CD4/CD8 比值和增加 SIgA 的产生来介导和改善肠道免疫功能。
