| Project/Area Number |
18K08879
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
Okada Motoi 旭川医科大学, 医学部, 准教授 (80431427)
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| Co-Investigator(Kenkyū-buntansha) |
藤田 智 旭川医科大学, 医学部, 名誉教授 (10173428)
井尻 えり子 旭川医科大学, 大学病院, 助教 (40646072)
川口 哲 旭川医科大学, 医学部, 助教 (60814217)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 敗血症 / 心不全 / β３受容体 / エンドトキシン / ミトコンドリア / NO産生 / 心筋代謝 / LPS / 敗血症性心筋症 / メタボリックシフト |
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| Outline of Final Research Achievements |
In this study, we generated a mouse model of endotoxin (LPS)-induced heart failure, in which the myocardium is found to have increased expression of β3 receptors. The model showed a rapid decline in cardiac function and increased mortality, but administration of a β3 receptor antagonist restored cardiac function and prognosis, as well as reduced myocardial ATP levels. The mechanism for this was found to be abnormal transport of fatty acids into the mitochondria, although their uptake into the myocardium was preserved. Furthermore, inhibition of β3 receptors suppressed NFkB-mediated cytokine production, such as IL-6, and the induction of iNOS.
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| Academic Significance and Societal Importance of the Research Achievements |
予後不良疾患である敗血症による心不全の病態において、エンドトキシンによる心不全もでるでは、β3受容体を制御することで、心機能や生命予後を改善することが確認された。このことは、β３受容体が敗血症性心筋症への治療ターゲットになる可能性があると考えられる。
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