2019 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number	16K10972
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	Okayama 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
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
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.
Free Research Field	麻酔・蘇生学
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。