Rifaximin enhances the L‑carnitine‑mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut‑liver‑muscle axis

• 資料種別: 博士論文
• タイトル: Rifaximin enhances the L‑carnitine‑mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut‑liver‑muscle axis
• 著者・編者: Murata, Koji; Kaji, Kosuke; Nishimura, Norihisa; Enomoto, Masahide; Fujimoto, Yuki; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 著者標目: Murata, Koji; Kaji, Kosuke; Nishimura, Norihisa; Enomoto, Masahide; Fujimoto, Yuki; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 出版事項: Spandidos Publications
• 出版年月日等: 2022-08
• 出版年（W3CDTF）: 2022-08
• 並列タイトル等: リファキシミンは腸-肝臓-筋肉軸の調節により肝硬変ラットの骨格筋萎縮に対するL-カルニチンを介した予防効果を増強する
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2023-03-15
• 授与年月日（W3CDTF）: 2023-03-15
• 報告番号: 甲第863号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: liver cirrhosis; sarcopenia; endotoxin; intestinal permeability
• 対象利用者: 一般
• 一般注記: type:Thesis; The gut‑liver‑muscle axis is associated with thedevelopment of sarcopenia in liver cirrhosis. The presentstudy aimed to illustrate the combined effects of rifaximinand L‑carnitine on skeletal muscle atrophy in cirrhotic ratswith steatohepatitis. For this purpose, a total of 344 Fischerrats were fed a choline‑deficient L‑amino acid‑defined(CD AA) diet with the daily oral administration of rifaximin(100 mg/kg) and/or L‑carnitine (200 mg/kg), and measurementsof psoas muscle mass index and forelimb grip strengthwere performed. After feeding for 12 weeks, blood samples,and liver, ileum and gastrocnemius muscle tissues wereharvested. The effects of L‑carnitine on rat myocytes wereassessed using in vitro assays. Treatment with rifaximinattenuated hyperammonemia and liver fibrosis in theCD AA‑fed rats. Moreover, it improved intestinal permeabilitywith the restoration of tight junction proteins andsuppressed the lipopolysaccharide (LPS)‑mediated hepaticmacrophage activation and pro‑inflammatory response. Inaddition, rifaximin prevented skeletal muscle mass atrophyand weakness by decreasing intramuscular myostatin andpro‑inflammatory cytokine levels. Moreover, rifaximinsynergistically enhanced the L‑carnitine‑mediated improvementof skeletal muscle wasting by promoting the productionof insulin‑like growth factor‑1 and mitochondrial biogenesis,resulting in the inhibition of the ubiquitin‑proteasome system(UPS). The in vitro assays revealed that L‑carnitine directlyattenuated the impairment of mitochondrial biogenesis,thereby inhibiting the UPS in rat myocytes that were stimulatedwith LPS or tumor necrosis factor‑α. On the whole, thepresent study demonstrates that the combination of rifaximinwith L‑carnitine may provide a clinical benefit for livercirrhosis‑related sarcopenia.; 博士（医学）・甲第863号・令和5年3月15日; © Murata et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.; identifier:International journal of molecular medicine Vol.50 No.2 Article No.101 (2022 Aug); identifier:11073756; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4095; identifier:International journal of molecular medicine, 50(2): Article No.101
• 国立国会図書館永続的識別子: info:ndljp/pid/13120249; https://dl.ndl.go.jp/pid/13120249
• 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）: 2023-12-05T21:41:08+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
• 掲載誌（URI）: http://hdl.handle.net/10564/4095
• 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