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J-GLOBAL ID：202102268842323602   整理番号：21A2258266

定量的プロテオミクスは代謝改善がイソプロテレノール誘発心臓傷害に対するT89の心臓保護効果に寄与する【JST・京大機械翻訳】

Quantitative Proteomics Reveal That Metabolic Improvement Contributes to the Cardioprotective Effect of T₈₉ on Isoproterenol-Induced Cardiac Injury

著者 (79件)： Wei Xiao-Hong (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  Wei Xiao-Hong (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Wei Xiao-Hong (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Wei Xiao-Hong (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Wei Xiao-Hong (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Wei Xiao-Hong (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Guo Xiao (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  Guo Xiao (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Guo Xiao (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Guo Xiao (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Guo Xiao (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Guo Xiao (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Pan Chun-Shui (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Pan Chun-Shui (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Pan Chun-Shui (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Pan Chun-Shui (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Pan Chun-Shui (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Li Huan (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  Li Huan (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Li Huan (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Li Huan (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Li Huan (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Li Huan (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Cui Yuan-Chen (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Cui Yuan-Chen (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Cui Yuan-Chen (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Cui Yuan-Chen (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Cui Yuan-Chen (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Yan Li (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Yan Li (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Yan Li (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Yan Li (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Yan Li (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Fan Jing-Yu (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Fan Jing-Yu (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Fan Jing-Yu (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Deng Jing-Na (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Deng Jing-Na (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Deng Jing-Na (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Deng Jing-Na (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Deng Jing-Na (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Hu Bai-He (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Hu Bai-He (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Hu Bai-He (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Hu Bai-He (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Hu Bai-He (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Chang Xin (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Chang Xin (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Chang Xin (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Chang Xin (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Chang Xin (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  He Shu-Ya (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  He Shu-Ya (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  He Shu-Ya (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  He Shu-Ya (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  He Shu-Ya (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  He Shu-Ya (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Yan Lu-Lu (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Yan Lu-Lu (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Yan Lu-Lu (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Yan Lu-Lu (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Yan Lu-Lu (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Sun Kai (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Sun Kai (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Sun Kai (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Sun Kai (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Sun Kai (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Wang Chuan-She (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  Wang Chuan-She (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Wang Chuan-She (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Wang Chuan-She (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Wang Chuan-She (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Wang Chuan-She (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China) ,  Han Jing-Yan (Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China) ,  Han Jing-Yan (Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China) ,  Han Jing-Yan (Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China) ,  Han Jing-Yan (Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Han Jing-Yan (Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China) ,  Han Jing-Yan (State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China)
資料名： Frontiers in Physiology (Web)  (Frontiers in Physiology (Web))
巻： 12  ページ： 653349  発行年： 2021年 
JST資料番号： U7093A  ISSN： 1664-042X  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： スイス (CHE)  言語： 英語 (EN)

抄録/ポイント： 背景:漢方薬であるT_89は第II相を通過し,米国FDAによる虚血性心血管疾患の治療に対する第III相臨床試験を受けている。しかし,イソプロテレノール(ISO)誘導心臓損傷に対するT_89の役割は知られていない。本研究は,ISO誘発心臓損傷に対するT_89の効果と根底にある機構を探ることを目的とした。【方法】雄のSprague-Dawleyラットに,最初の3日間24時間間隔でISO食塩水を皮下注射し,次に次の12日間48時間間隔で投与した。111.6および167.4mg/kgの用量のT_89を15日間連続投与して投与した。ラット生存率,心機能評価,形態学的観察,定量的プロテオミクス,およびウェスタンブロット法分析を行った。【結果】T_89は明らかにISO誘発低生存率を改善し,心筋血流,心臓機能,および形態によって証明されたように,ISO誘発心臓損傷を減弱した。定量的プロテオミクスは,T_89の心臓保護効果が糖脂質代謝とエネルギー代謝を含む代謝経路の調節に依存することを明らかにした。T_89は,解糖の増強を阻害し,脂肪酸酸化を促進し,Eno1,Mcee,Bdh1,Ces1c,Apoc2,Decr1,Acaa2,Cbr4,ND2,Cox6a,Cox17,ATP5g,およびATP5jの調節によりミトコンドリア酸化リン酸化を回復させ,その結果,酸化ストレスとエネルギー代謝障害を軽減し,ISO後の心臓損傷を改善した。本研究はまた,T_89がHSP70/HSP40のISO誘導増加を有意に抑制し,ERKのリン酸化を抑制し,さらにCX43の発現を回復させ,心臓肥大におけるT_89の保護的役割を確認した。プロテオミクスデータは,識別子PXD024641によるプロテオームX変化を介して利用可能である。結論:T_89は死亡率を低下させ,ISO誘発心臓損傷のモデルにおける転帰を改善し,T_89の心保護的役割は,糖脂質代謝の調節,ミトコンドリア機能の回復,および心筋エネルギーの改善と相関する。Copyright 2021 The Author(s) All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 酸化 ,  *心臓 ,  心筋 ,  皮下投与 ,  ミトコンドリア ,  ラット ,  リン酸化 ,  虚血 ,  生存率 ,  心臓肥大 ,  反復投与 ,  酸化ストレス ,  ウェスタンブロット法 ,  *プロテオミクス ,  カテコールアミン ,  アミノアルコール ,  第二アミン ,  第二アルコール

著者キーワード (5件)： 解糖 ,  脂肪酸酸化 ,  エネルギー代謝 ,  ミトコンドリア電子伝達鎖 ,  心臓肥大

分類 (2件)： 生薬の薬理の基礎研究  (GX06020J) ,  心臓作用薬の基礎研究  (GW07020N)

物質索引 (1件)： イソプロテレノール

引用文献 (41件)：

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タイトルに関連する用語 (7件)： 定量的プロテオミクス ,  代謝改善 ,  イソプロテレノール ,  誘発 ,  心臓 ,  傷害 ,  保護効果