Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis

• 資料種別: 博士論文
• タイトル: Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis
• 著者・編者: Enomoto, Masahide; Kaji, Kosuke; Nishimura, Norihisa; Fujimoto, Yuki; Murata, Koji; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Tanaka, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 著者標目: Enomoto, Masahide; Kaji, Kosuke; Nishimura, Norihisa; Fujimoto, Yuki; Murata, Koji; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Tanaka, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 出版事項: Elsevier
• 出版年月日等: 2022-10
• 出版年（W3CDTF）: 2022-10
• 並列タイトル等: リファキシミンとルビプロストンの併用は脂肪性肝炎ラットの腸管バリア機能を修復し肝線維化を抑制する
• タイトル（掲載誌）: Digestive and liver Disease
• 巻号年月日等（掲載誌）: 54 10
• 掲載巻: 54
• 掲載号: 10
• 掲載ページ: 1392-1402
• ISSN（掲載誌）: ISSN : 1590-8658
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2023-03-15
• 報告番号: 甲第860号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: Gut-liver axis; Lipopolysaccharide; Microbiome; Non-alcoholic steatohepatitis
• 対象利用者: 一般
• 一般注記: type:Thesis; Background: Although gut-derived lipopolysaccharide (LPS) affects the progression of non-alcoholic steatohepatitis (NASH) pathogenesis, few studies have focused on this relationship to develop treatments for NASH. Aims: To explore the effects of combination with rifaximin and lubiprostone on NASH liver fibrosis through the modulation of gut barrier function. Methods: To induce steatohepatitis, F344 rats were fed a choline-deficient l -amino acid-defined (CDAA) diet for 12 weeks and received oral administration of rifaximin and/or lubiprostone. Histological, molec- ular, and fecal microbial analyses were performed. Barrier function in Caco-2 cells were assessed by in vitro assays. Results: Combination rifaximin/lubiprostone treatment significantly suppressed macrophage expansion, proinflammatory responses, and liver fibrosis in CDAA-fed rats by blocking hepatic translocation of LPS and activation of toll-like receptor 4 signaling. Rifaximin and lubiprostone improved intestinal perme- ability via restoring tight junction proteins (TJPs) with the intestinal activation of pregnane X receptor and chloride channel-2, respectively. Moreover, this combination increased the abundance of Bacteroides, Lactobacillus, and Faecalibacterium as well as decreased that of Veillonella resulting in an increase of fecal short-chain fatty acids and a decrease of intestinal sialidase activity. Both agents also directly suppressed the LPS-induced barrier dysfunction and depletion of TJPs in Caco-2 cells. Conclusion: The combination of rifaximin and lubiprostone may provide a novel strategy for treating NASH-related fibrosis.; 博士（医学）・甲第860号・令和5年3月15日; identifier:Digestive and liver disease Vol.54 No.10 p.1392-1402 (2022 Oct); identifier:15908658; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4091; identifier:Digestive and liver Disease, 54(10): 1392-1402
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1016/j.dld.2022.04.012
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4091/1/01%e7%94%b2860%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4091/2/02%e7%94%b2860%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4091/8/03%e7%94%b2860%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4091/7/04%e7%94%b2860Fig..pdf fulltext