Project/Area Number |
17K11050
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Anesthesiology
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
KOJIMA Akiko 滋賀医科大学, 医学部, 講師 (50447877)
|
Co-Investigator(Kenkyū-buntansha) |
北川 裕利 滋賀医科大学, 医学部, 教授 (50252391)
松浦 博 滋賀医科大学, 医学部, 理事 (60238962)
|
Project Period (FY) |
2017-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 吸入麻酔薬 / 心筋保護効果 / Ca2+制御タンパク質 / 虚血再灌流傷害 / 麻酔学 / イオンチャネル |
Outline of Final Research Achievements |
Ischemia-reperfusion injury, which occurs upon reperfusion of ischemic myocardium, is a myocardial injury primarily caused by intracellular Ca2+ overload. We have previously investigated the molecular mechanism underlying the occurrence of the oxygen paradox and Ca2+ paradox, which are experimental cellular models of myocardial ischemia-reperfusion injury, using normal mouse ventricular myocytes. We found that the dysfunction of Ca2+ handling proteins, such as RyR2 and SOCE channel, caused the abnormality in intracellular Ca2+ homeostasis, leading to cellular injury. In this study, we found that the development of the oxygen paradox in the hypertrophic cardiomyocytes was exaggerated, compared with normal cardiomyocytes.
|
Academic Significance and Societal Importance of the Research Achievements |
吸入麻酔薬の心筋保護作用の検討の多くは、prosurvival signaling pathwayに着目して行われてきたが、我々がこれまでに明らかにしてきた吸入麻酔薬の心筋保護作用のメカニズムは、Ca2+制御タンパク質(RyR2やSOCEチャネル、CaMKII)を標的としたものである。肥大心や不全心においてはSOCEチャネルタンパク質の発現増加やRyR2の機能亢進が報告されているため、正常心のみならず病態心における虚血再灌流傷害に対しても、セボフルランの心保護効果が期待できる。本研究成果は、吸入麻酔薬の保護作用を応用した新規の心筋保護法や心筋保護薬の開発に寄与すると期待される。
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