| Project/Area Number |
17K08536
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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 physiology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小嶋 亜希子 滋賀医科大学, 医学部, 講師 (50447877)
星野 真介 滋賀医科大学, 医学部, 助教 (70747576)
林 維光 滋賀医科大学, 医学部, 助教 (80242973)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | TRPCチャネル / 心筋虚血再灌流傷害 / Ca2+過負荷 / TAC手術 / 肥大心 / 不全心 / Ca2+/カルモジュリン依存性タンパク質キナーゼ / リアノジン受容体 / H2O2 / 遅延後脱分極 / Ca2+/CaMKII / KN-93 / 2-APB / La3+ / 心肥大 / 心不全 |
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| Outline of Final Research Achievements |
The present experiments using Langendorff-perfused mouse heart model revealed that transient receptor potential canonocal (TRPC) channel blockers improve left ventricular contractile function after ischemia/reperfusion, indicating that TRPC channels are responsible for mediating the development of ischemia/reperfusion injury in the heart. In addition, patch-clamp experiments found that hydrogen peroxide (H2O2), which acts as a critical trigger for ischemia/reperfusion injury, evoked delayed after-depolarizations (DADs) at a higher frequency in hypertrophied left ventricular myocytes produced by transverse aortic constriction (TAC) operation than in normal ventricular myocytes. These results indicate that intracellular Ca2+ overload more readily occurs in hypertrophied heart than in normal heart during ischemia/reperfusion. The present investigation also found that calcium/calmodulin-dependent protein kinase II mediates the occurrence of DADs in hypertrophied left ventricular myocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題の成果により、臨床における閉塞冠動脈の再疎通療法時などの虚血再灌流傷害が発生しうる状況下において、TRPC (transient receptor potential canonical) チャネル阻害薬が心筋保護作用をもつ可能性が示唆された。今後さらに基礎実験を重ねていき、TRPCチャネル阻害薬の心筋保護作用に関わる分子機構を明らかにして、TRPCチャネル阻害薬が臨床における虚血性心疾患の予後改善に寄与できる可能性について検討を重ねる必要がある。
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