Combining probiotics and an angiotensin-II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non-alcoholic steatohepatitis. 3

• 資料種別: 博士論文
• タイトル: Combining probiotics and an angiotensin-II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non-alcoholic steatohepatitis.
• 巻次・部編番号: 49 3
• 著者・編者: Sawada, Yasuhiko; Kawaratani, Hideto; Kubo, Takuya; Fujinaga, Yukihisa; Furukawa, Masanori; Saikawa, Soichiro; Sato, Shinya; Seki, Kenichiro; Takaya, Hiroaki; Okura, Yasushi; Kaji, Kosuke; Shimozato, Naotaka; Mashitani, Tsuyoshi; Kitade, Mitsuteru; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yamao, Junichi; Yoshiji, Hitoshi
• 著者標目: Sawada, Yasuhiko; Kawaratani, Hideto; Kubo, Takuya; Fujinaga, Yukihisa; Furukawa, Masanori; Saikawa, Soichiro; Sato, Shinya; Seki, Kenichiro; Takaya, Hiroaki; Okura, Yasushi; Kaji, Kosuke; Shimozato, Naotaka; Mashitani, Tsuyoshi; Kitade, Mitsuteru; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yamao, Junichi; Yoshiji, Hitoshi
• 出版事項: Wiley
• 出版年月日等: 2019-03; 49 3
• 出版年（W3CDTF）: 2019-03
• 並列タイトル等: ラット非アルコール性脂肪肝炎モデルに対するプロバイオティクスとアンギオテンシンⅡ受容体拮抗薬併用療法の肝線維化に対する有効性
• タイトル（掲載誌）: Hepatology research
• 掲載ページ: 284-295
• ISSN（掲載誌）: 13866346
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2020-09-30
• 授与年月日（W3CDTF）: 2020-09-30
• 報告番号: 乙第1465号
• 学位: 博士（医学）
• 博論授与番号: 乙第1465号
• 本文の言語コード: eng
• 件名標目: angiotensin‐II type 1 receptor blocker (ARB); hepatic fibrosis; intestinal tight junction; non‐alcoholic steatohepatitis; probiotic
• 対象利用者: 一般
• 一般注記: type:Thesis; Aim: Intestinal endotoxin is important for the progression of non-alcoholic steatohepatitis (NASH). Circulating endotoxin levels are elevated in most animal models of diet-induced non-alcoholic fatty liver disease (NAFLD) and NASH. Furthermore, plasma endotoxin levels are significantly higher in NAFLD patients, which is associated with small intestinal bacterial overgrowth and increased intestinal permeability. By improving the gut microbiota environment and restoring gut-barrier functions, probiotics are effective for NASH treatment in animal models. It is also widely known that hepatic fibrosis and suppression of activated hepatic stellate cells (Ac-HSCs) can be attenuated using an angiotensin-II type 1 receptor blocker (ARB). We thus evaluated the effect of combination probiotics and ARB treatment on liver fibrosis using a rat model of NASH. Methods: Fisher 344 rats were fed a choline-deficient/L-amino acid-defined (CDAA) diet for 8 weeks to generate the NASH model. Animals were divided into ARB, probiotics, and ARB plus probiotics groups. Therapeutic efficacy was assessed by evaluating liver fibrosis, the lipopolysaccharide Toll-like receptor (TLR)4 regulatory cascade, and intestinal barrier function. Results: Both probiotics and ARB inhibited liver fibrosis, with concomitant HSC activation and suppression of liver-specific transforming growth factor-β and TLR4 expression. Probiotics reduced intestinal permeability by rescuing zonula occludens-1 disruption induced by the CDAA diet. Angiotensin-II type 1 receptor blocker was found to directly suppress Ac-HSCs. Conclusions: Probiotics and ARB are effective in suppressing liver fibrosis through different mechanisms. Currently both drugs are in clinical use; therefore, the combination of probiotics and ARB is a promising new therapy for NASH.; 博士（医学）・乙第1465号・令和2年9月30日; © 2018 The Japan Society of Hepatology; This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.13281], which has been published in final form at [https://doi.org/10.1111/hepr.13281]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.; identifier:Hepatology research Vol.49 No.3 p.284-295 (2020 Mar); identifier:13866346; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3781; identifier:Hepatology research, 49(3): 284-295
• 国立国会図書館永続的識別子: info:ndljp/pid/11583359; https://dl.ndl.go.jp/pid/11583359
• 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）: 2020-12-08T06:37:43+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/10.1111/hepr.13281
• 掲載誌（URI）: http://hdl.handle.net/10564/3781
• 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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