| Project/Area Number |
16K01384
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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 |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
YADA TOYOTAKA 川崎医科大学, 医学部, 講師 (00210279)
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| Co-Investigator(Kenkyū-buntansha) |
小笠原 康夫 川崎医療福祉大学, 医療技術学部, 教授 (10152365)
仲本 博 川崎医科大学, 医学部, 助教 (10299183)
佐々木 環 川崎医科大学, 医学部, 教授 (30187124)
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| Research Collaborator |
Shimokawa Hiroaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 内皮依存性過分極 / 過酸化水素 / caveolin-1 / 一酸化窒素 / 心内膜側微小血管 / 血管内皮 / 近赤外線蛍光顕微鏡 / 糖尿病 / 冠微小血管 / 心筋虚血 / 側副血行路 / 冠血管予備能 / 内皮由来過分極 / 冠微小循環障害 / 心内膜側 / 虚血 |
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| Outline of Final Research Achievements |
We examined the endothelium-dependent hyperpolarization (EDH)-mediated responses to compensate reduced nitric oxide (NO)-mediated responses in diabetes mellitus (DM) during occlusion in dogs in vivo. Canine subepicardial and subendocardial collateral coronary small arteries (CSA>100 micrometer) and arterioles (CA<100 micrometer) were observed by an infrared fluorescence microscope. Experiments were performed during occlusion of the left anterior descending coronary artery (LAD 90 min). Caveolin-1 in the LAD area were greater in coronary microvessels than in conduit arteries in the control. NO-mediated vasodilations of CSA to bradykinin did not increase in DM (before and after coronary occlusion at 85 min) associated with decreased eNOS phosphorylation at Ser1177 compared with baseline controls, and were restored by compensation of EDH, and were suppressed by KCa channel blockade.
NO-mediated vasodilations of CSA during occlusion are compensated by EDH of CA in dogs of DM in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
当教室で応用開発した近赤外線蛍光顕微鏡を用いて、糖尿病性心筋虚血モデルの心内膜側冠微小循環及び冠動脈側副血行路の血管拡張効果を評価し、内皮依存性血流調節因子の定量評価を行い、心内膜側虚血発症及び側副血行路血流改善の両メカニズムを解明する。冠動脈の豊富な側副血行路を検出し、術後虚血性冠微小循環障害を改善し、内皮機能改善薬が、内因性過酸化水素と一酸化窒素を介した血行改善を認める事が予想される。
これらが実証されれば、冠微小循環障害や冠微小側副血行路血流の改善評価を可能にする診断治療に発展する基礎的研究となり、将来的にヒト冠動脈バイパス術への応用も可能で重要な学術的意義がある。
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