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The role of mitophagy in the therapy of CO-releasing molecule against acute respiratory distress syndrome

Research Project

Project/Area Number 16K10972
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionOkayama Prefectural University

Principal Investigator

Takahashi Toru  岡山県立大学, 保健福祉学部, 教授 (40252952)

Co-Investigator(Kenkyū-buntansha) 森松 博史  岡山大学, 医歯薬学総合研究科, 教授 (30379797)
清水 裕子  岡山大学, 医学部, 客員研究員 (80423284)
荻野 哲也  岡山県立大学, 保健福祉学部, 教授 (90252949)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords出血性ショック / 蘇生後肺傷害 / 炎症反応 / 一酸化炭素 / CO遊離分子 / 抗炎症薬 / 蘇生後急性肺傷害 / 炎症 / アポトーシス / インフラマソーム / 抗炎症療法 / 抗炎症性サイトカイン / COヘモグロビン / CO-releasing molecule / TUNEL陽性細胞 / カスパーゼ / 炎症性サイトカイン / 抗炎症作用 / ARDS / 出血性ショック蘇生 / CO releasing molecule / マイトファジー
Outline of Final Research Achievements

Even after successful resuscitation, hemorrhagic shock due to trauma and massive surgical bleeding, etc.,is known to induce a pulmonary inflammatory response that leads to acute lung injury, which is referred to as acute respiratory distress syndrome (ARDS). Although lung protective ventilation has been proposed for the treatment of ARDS in clinical settings, there is no definitive pharmacological therapy to prevent pulmonary inflammation in ARDS. Carbon monoxide (CO) is widely known to be a toxic gaseous molecule that produces carboxyhemoglobin due to its higher affinity to hemoglobin. However,carbon monoxide-releasing molecule-3 (CORM-3) has been reported to liberate and deliver extremely low amount of CO under physiological conditions, which exerts organ-protective effects during systemic insults. In the present study, we demonstrated that CORM-3 confers protection against hemorrhagic shock-induced ARDS mediated through its anti-inflammatory property in rats.

Academic Significance and Societal Importance of the Research Achievements

重症肺炎に対する治療は、もちろん病原体に対する有効な薬物の投与を行うべきである。しかし、新型コロナウイルス肺炎のように病原体に対する有効な薬物が存在せず、かつ、過剰な免疫反応にともなう炎症がその重症化に寄与している場合、過剰な炎症反応を抑えることが非常に有効な治療法となりうる。本研究では、ラット出血性ショック蘇生後肺炎に対してCO遊離分子が有効なことを示した。CO遊離分子はまだ、臨床応用できる段階ではないが「重症新型コロナウイルス肺炎」に対する抗炎症薬となる可能性がある。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] Therapeutic effect of carbon monoxide releasing molecule 3 on acute lung injury after hemorrhagic shock and resuscitation2019

    • Author(s)
      YUTA KUMADA, TORU TAKAHASHI, HIROKO SHIMIZU, RYU NAKAMURA, EMIKO OMORI, KAZUYOSHI INOUE and HIROSHI MORIMATSU
    • Journal Title

      EXPERIMENTAL AND THERAPEUTIC MEDICINE

      Volume: 17 Pages: 3429-3440

    • DOI

      10.3892/etm.2019.7390

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury2017

    • Author(s)
      Yamaoka M, Shimizu H, Takahashi T, Omori E, Morimatsu H
    • Journal Title

      PLoS One

      Volume: 12 Issue: 7 Pages: e0180934-e0180934

    • DOI

      10.1371/journal.pone.0180934

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 呼気ガス:酸化ストレスの指標としての可能性2016

    • Author(s)
      高橋 徹
    • Journal Title

      ICUとCCU

      Volume: 40 Pages: 533-538

    • Related Report
      2016 Research-status Report
  • [Presentation] Protectove role of Carbon monoxide (CO)/CO-releasing molecule against acute respiratory distress syndrome induced by hemorrhagic shock and resuscitation2019

    • Author(s)
      Toru Takahashi, Yuta Kumada, Hiroko Shimizu and Hiroshi Morimatsu
    • Organizer
      23th International Symposium on Molecular Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Significant changes in renal Bach1 expression in rhabdomyolysis-induced aute kidney injury2017

    • Author(s)
      Toru Takahashi, Masakazu Yamaoka, Hiroko Shimizu and Hiroshi Moromatsu
    • Organizer
      20th International Symposium on Molecular Medicine
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Carbon Monoxide-Releasing Molecule-3 Ameliorates Lung Injury after Hemorrhagic Shock and Resuscitation2017

    • Author(s)
      Yuta Kumada, Hiroko Shimizu, Ryu Nakamura, Emiko Omori, Kazuyoshi Inoue, Toru Takahashi, Hiroshi Morimatsu
    • Organizer
      The Anesthesiology Annual Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of Bach1 mRNA in a rat model of acute liver injury2016

    • Author(s)
      Toru Takahashi
    • Organizer
      19th International Symposium on Molecular Medicine
    • Place of Presentation
      Athens, Greece
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] エンドトキシン・自然免疫研究2016

    • Author(s)
      高橋 徹
    • Publisher
      医学図書出版株式会社
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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