| Project/Area Number |
17K17956
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
General pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | コルヒチン / 心筋梗塞 / 炎症 / インフラマソーム / 左室リモデリング / NLRP3インフラマソーム / リモデリング |
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| Outline of Final Research Achievements |
Administration of colchicine to mouse model of acute myocardial infarction attenuated the decrease of cardiac function after myocardial infarction, and improved heart failure and mortality during the chronic phase. Histopathological examination revealed that colchicine suppressed excessive accumulation of inflammatory cells and the production of pro-inflammatory cytokines in the infarcted myocardium. Inhibition of pro-inflammatory cytokines was observed in the infarcted myocardium, rather than systemically, suggesting colchicine inhibited local inflammation after myocardial infarction. It was suggested that the anti-inflammatory mechanism of colchicine might be mediated via the NLRP3 inflammasome cascade.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、コルヒチンが梗塞心筋局所の過剰な炎症反応を抑制し、それにはNLRP3インフラマソームを介した炎症抑制メカニズムが関与する可能性を初めて示した。本研究結果は今後の心血管疾患の新たな治療開発に影響を与えるものと考えられる。しかし、NLRP3インフラマソーム阻害モデルを用いた検証が不十分であること、また血管の炎症抑制効果の検討は不十分であることから引き続き心血管領域におけるコルヒチンの抗炎症作用のメカニズムについて検証を続けていく。
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