Gut-liver axis mediated by endotoxin and innate immunity

内毒素和先天免疫介导的肠肝轴

• 批准号: 23590987
• 负责人: FUKUI HIROSHI
• 金额: $ 2.83万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590987/
• 关键词: エンドトキシン; 自然免疫; Toll-like受容体; 非アルコール性脂肪肝炎; 腸管相関; 難吸収性抗菌薬; ウルソデオキシコール酸; 急性肝不全; TNF-α

The underling cause of nonalcoholic steatohepatitis is still unlear, but intestinal bacterial flora and endotoxin are important factors. We evaluated pathogenic roles of endotoxin, intestinal permeability and innate immunity on the development of liver fibrosis in rats fed choline-deficient and amino acid-defined (CDAA) diet. In these rats, marked fibrosis was associated with increased intestinal permeability, augmented development of Toll-like recrptor 4 (TLR4) mRNA, lipopolysaccharide binding protein (LBP) mRNA and TNF-alpha mRNA in the liver. Oral administrations of nonabsorbable antibiotics for selective bowel decontamination and ursodeoxycholic acids were demonstrated to suppress intestinal permeability and TLR4 mediated inflammation and finally inhibit progression of fibrosis. Regulation of gut-liver axis may become a new strategy for prevention of human steatohepatitis.

非酒精性脂肪性肝炎的病因尚不清楚，但肠道菌群植物群和内毒素是重要因素。我们评估了内毒素、肠道通透性和先天免疫在胆碱缺乏和氨基酸限定（CDAA）饮食大鼠肝纤维化发展中的致病作用。在这些大鼠中，显著的纤维化与肠通透性增加、肝脏中Toll样受体4（TLR 4）mRNA、脂多糖结合蛋白（LBP）mRNA和TNF-α mRNA的增加有关。口服非吸收性抗生素进行选择性肠道去污和熊去氧胆酸被证明可以抑制肠道通透性和TLR 4介导的炎症，并最终抑制纤维化的进展。调节肠-肝轴可能成为预防人类脂肪性肝炎的新策略。

项目成果

自然免疫制御による肝線維化の抑制：小腸Tight Junction Proteinの役割

通过先天免疫调节抑制肝纤维化：小肠紧密连接蛋白的作用

• 发表时间: 2014
• 作者: 堂原 彰敏;吉治 仁志;福井 博
• 通讯作者: 福井 博

Therapeutic effect of cytokine modulator Y-40138 in the rat alcoholic liver disease model

细胞因子调节剂Y-40138对大鼠酒精性肝病模型的治疗作用

• 发表时间: 2012
• 作者: Kawaratani H;Tsujimoto T;Moriya K;Douhara A;Takaya H;Mitoro A;Yoshiji H;Uemura M;Fukui H.
• 通讯作者: Fukui H.

Potential role of endotoxemia on the decreased activity of plasma ADAMTS13 in patients with chronic and acute hepatic failure

内毒素血症对慢性和急性肝衰竭患者血浆 ADAMTS13 活性降低的潜在作用

• 发表时间: 2012
• 作者: Takaya H;Uemura M;Fujimoto M;Matsuyama T;Morioka C;Ishikawa M;Kawaratani H;Matsumoto M;Fujimura Y;Fukui H.
• 通讯作者: Fukui H.

ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score

• DOI: 10.1111/j.1872-034x.2011.00950.x
• 发表时间: 2012-05-01
• 期刊: HEPATOLOGY RESEARCH
• 影响因子: 4.2
• 作者: Takaya, Hiroaki;Uemura, Masahito;Fukui, Hiroshi
• 通讯作者: Fukui, Hiroshi

Difficulty in evaluating intestinal permeability in patients with liver cirrhosis: What is the precipitating factor?

肝硬化患者肠道通透性评估困难：诱发因素是什么？

• DOI: 10.1111/j.1872-034x.2012.01104.x
• 发表时间: 2013
• 期刊: Hepatol Res
• 影响因子: 4.2
• 作者: 藤田尚己;宮地洋英;杉本龍亮;諸岡留美;田中秀明, 長徹二;坂保寛;原田雅典;岩佐元雄;長谷川浩司;竹井謙之;Fukui H
• 通讯作者: Fukui H