| Project/Area Number |
17K08586
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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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| Research Field |
General pharmacology
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| Research Institution | Health Sciences University of Hokkaido (2019)
University of Toyama (2017-2018) |
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Principal Investigator |
HATTORI Yuichi 北海道医療大学, その他, 客員教授 (50156361)
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| Co-Investigator(Kenkyū-buntansha) |
大橋 若奈 富山大学, 学術研究部医学系, 助教 (50381596)
冨田 賢吾 富山大学, 大学院医学薬学研究部(医学), 助教 (20758213)
鈴木 登紀子 富山大学, 大学院医学薬学研究部(医学), 助教 (10415531)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 敗血症 / 播種性血管内凝固 / 転写因子 / 薬理学 / 転与因子 |
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| Outline of Final Research Achievements |
We used the cecal ligation and puncture (CLP)-induced sepsis mouse model. In septic mice, the mRNA expression levels of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) were greatly increased. In addition, the number of platelets in CLP-induced septic mice were markedly reduced and prothrombin time was significantly prolonged in CLP mice in comparison with controls. These results imply that CLP-induced sepsis is a relevant model of sepsis-associated disseminated intravascular coagulation (DIC). Transfection of NF-κB decoy oligodeoxynucleotides via intravenous injection, when given 1 h after CLP, resulted in a striking reduction in the DNA binding of NF-κB in lungs at 6 h and strongly inhibited elevations in blood levels of pro-inflammatory cytokines in CLP mice. However, NF-κB decoy transfection failed to affect the changes in measures as DIC in CLP mice, suggesting no involvement of the transcription factor NF-κB in the molecular mechanisms underlying septic DIC.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により，盲腸結紮穿孔敗血症マウスは敗血症性DIC病態を研究するうえでよいモデルであることを明らかにした。本研究は，敗血症によるDICの分子病態機構の解明に新たな展開を与えるとともに，現時点で確立されたよい治療法の全くない本病態において，新たなDIC発症予防の開発を模索していくうえでも意義のある研究となったと考えられる。
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