Effective Combination Therapy of Angiotensin-II Receptor Blocker and Rifaximin for Hepatic Fibrosis in Rat Model of Nonalcoholic Steatohepatitis. 15

• 資料種別: 博士論文
• タイトル: Effective Combination Therapy of Angiotensin-II Receptor Blocker and Rifaximin for Hepatic Fibrosis in Rat Model of Nonalcoholic Steatohepatitis.
• 巻次・部編番号: 21 15
• 著者・編者: Fujinaga, Yukihisa; Kawaratani, Hideto; Kaya, Daisuke; Tsuji, Yuki; Ozutsumi, Takahiro; Furukawa, Masanori; Kitagawa, Koh; Sato, Shinya; Nishimura, Norihisa; Sawada, Yasuhiko; Takaya, Hiroaki; Kaji, Kosuke; Shimozato, Naotaka; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 著者標目: Fujinaga, Yukihisa; Kawaratani, Hideto; Kaya, Daisuke; Tsuji, Yuki; Ozutsumi, Takahiro; Furukawa, Masanori; Kitagawa, Koh; Sato, Shinya; Nishimura, Norihisa; Sawada, Yasuhiko; Takaya, Hiroaki; Kaji, Kosuke; Shimozato, Naotaka; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2020-08-04; 21 15
• 出版年（W3CDTF）: 2020-08-04
• 並列タイトル等: ラットを用いた非アルコール生脂肪肝炎におけるアンジオテンシンⅡ受容体拮抗薬とリファキシミン併用薬投与による肝線維化抑制効果の検討
• タイトル（掲載誌）: International journal of molecular sciences
• 掲載ページ: Article No.5589-
• ISSN（掲載誌）: 14220067
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2021-03-15
• 授与年月日（W3CDTF）: 2021-03-15
• 報告番号: 甲第780号
• 学位: 博士（医学）
• 博論授与番号: 甲第780号
• 本文の言語コード: eng
• 件名標目: hepatic fibrosis; rifaximin; ARB; metabolic syndrome; NASH
• 対象利用者: 一般
• 一般注記: type:Thesis; The progression of nonalcoholic steatohepatitis (NASH) is complicated. The multiple parallel-hits theory is advocated, which includes adipocytokines, insulin resistance, endotoxins, and oxidative stress. Pathways involving the gut-liver axis also mediate the progression of NASH. Angiotensin-II receptor blockers (ARB) suppress hepatic fibrosis via the activation of hepatic stellate cells (HSCs). Rifaximin, a nonabsorbable antibacterial agent, is used for the treatment of hepatic encephalopathy and has been recently reported to improve intestinal permeability. We examined the inhibitory effects on and mechanism of hepatic fibrogenesis by combining ARB and rifaximin administration. Fischer 344 rats were fed a choline-deficient/l-amino acid-defined (CDAA) diet for 8 weeks to generate the NASH model. The therapeutic effect of combining an ARB and rifaximin was evaluated along with hepatic fibrogenesis, the lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade, and intestinal barrier function. ARBs had a potent inhibitory effect on hepatic fibrogenesis by suppressing HSC activation and hepatic expression of transforming growth factor-β and TLR4. Rifaximin reduced intestinal permeability by rescuing zonula occludens-1 (ZO-1) disruption induced by the CDAA diet and reduced portal endotoxin. Rifaximin directly affect to ZO-1 expression on intestinal epithelial cells. The combination of an ARB and rifaximin showed a stronger inhibitory effect compared to that conferred by a single agent. ARBs improve hepatic fibrosis by inhibiting HSCs, whereas rifaximin improves hepatic fibrosis by improving intestinal permeability through improving intestinal tight junction proteins (ZO-1). Therefore, the combination of ARBs and rifaximin may be a promising therapy for NASH fibrosis.; 博士（医学）・甲第780号・令和3年3月15日; © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:International journal of molecular sciences Vol.21 No.15 Article No.5589 (2020 Aug); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3904; identifier:International journal of molecular sciences, 21(15): Article No.5589
• 国立国会図書館永続的識別子: info:ndljp/pid/12070981; https://dl.ndl.go.jp/pid/12070981
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2022-02-06T04:33:19+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 関連情報（URI）: https://doi.org/10.3390/ijms21155589
• 掲載誌（URI）: http://hdl.handle.net/10564/3904
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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