Pathologic elucidation of sepsis by suppressing NET formation: focus on tissue factor and autophagy
| Project/Area Number |
17K11064
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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 |
Anesthesiology
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| Research Institution | Nagoya City University (2022)
Fujita Health University (2017-2021) |
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Principal Investigator |
SHIMOMURA Yasuyo 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (80534031)
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| Co-Investigator(Kenkyū-buntansha) |
西田 修 藤田医科大学, 医学部, 教授 (20208185)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 敗血症 / NETs / Autophagy / 多臓器不全 / DIC / 好中球細胞外トラップス / トロンボモジュリン / 敗血症性DIC / ヒストン / 敗血性ショック / オートファジー / 免疫学 / 感染症 / トランスレーショナルリサーチ / 細胞・組織 |
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| Outline of Final Research Achievements |
Activity of Autophagy with neutrophils and pathologic improvement in approximately 80% of patients with ICU admission serious case were observed, and it was predicted that activation of Autophagy could be expected to improve the condition.
We used the LPS-induced murine septic shock model, rTM was administered after the LPS injection (rTM group) so that there was not estrangement with the clinical practice.The survival rate 72 hours after the LPS administration was improved from 50% to 100% in rTM group. In the rTM group, blood cytokine levels did not increase and NETs formation was reduced in various organs.These results suggest that rTM improved survival in LPS-induced sepsis model mice due to cytokine storm suppression and inhibition of NETs formation in various organs.Those data supported of publication (13 of international journals and 2 of Japanese journal), and the meeting presentation of 22 times (including 4 times of international societies).
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| Academic Significance and Societal Importance of the Research Achievements |
敗血症は感染を要因に臓器障害が起こり、呼吸や循環に異常をきたして、死に至る場合もあるため、集中治療室（ICU）での全身管理と治療が必要になる。通常は感染で生命の危機にさらされることはなく、敗血症の重症化には過剰な免疫反応が原因と言われいるが、その機序や治療法はまだ未知なことが多い。本研究では、敗血症DICの治療薬で抗凝固作用を有するトロンボモジュリンに、敗血症時の過剰な免疫反応の一つであるサイトカインの異常産生やNETs形成の抑制効果があることを示した。敗血症における免疫機序の一端を本研究で解明できたことは、治療法の今後の発展につながることが期待され、学術的・社会的意義があると考える。
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Report
(7 results)
Research Products
(37 results)
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[Journal Article] Suppressive effects of the neutrophil elastase inhibitor sivelestat sodium hydrate on interleukin-1β production in lipopolysaccharide-stimulated porcine whole blood2020
Author(s)
Yasuyoshi Kurimoto, Yasuyo Shimomura, Kazuhiro Moriyama, Tomoyuki Nakamura, Naohide Kuriyama, Yoshitaka Hara, Hidefumi Komura, Daisuke Hasegawa, Takahiro Kawaji, Osamu Nishida
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Journal Title
Fujita Medical Journal
Volume: 6
Issue: 1
Pages: 12-16
DOI
NAID
ISSN
2189-7247, 2189-7255
Related Report
Peer Reviewed / Open Access
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