| Project/Area Number |
16K10938
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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 | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐伯 昇 広島大学, 病院(医), 講師 (30325170)
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| Research Collaborator |
Mukaida Keiko
Otsuki Sachiko
Kondo Takashi
Yasuda Toshimichi
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 悪性高熱症 / 骨格筋筋小胞体 / 1型リアノジン受容体 / 細胞内カルシウム調節 / ヒト培養骨格筋細胞 / ダントロレン / Ca-induced Ca release / 遺伝子導入 / 骨格筋培養 / CICR速度 / RYR1 / Ca / 培養骨格筋細胞 / カルシウム動態 / RYR1受容体 / リアノジン受容体 / 骨格筋細胞 / 培養 |
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| Outline of Final Research Achievements |
Malignant hyperthermia (MH) predisposition is determined by the presence or absence of an increase in Ca-induced Ca release (CICR) rate using skinned fibers, and the residual muscle is cultured after this examination. The environmental temperature was changed and the kinetics of Ca was measured. The inhibitory effect of dantrolene was also examined. This was also examined for HEK cells into which a mutation of the MH causative gene RYR1 was introduced.
As a result, an increase in Ca concentration in skeletal muscle cells due to an increase in environmental temperature was confirmed in both cultured human skeletal muscle cells and HEK cells. Dantrolene reduced Ca concentration due to temperature increase in HEK cells and cultured skeletal muscle cells. We concluded that this agent may be effective in preventing the onset of MH.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性高熱症（MH）はいまだ原因が特定できない致死的疾患の一つである．そんな中でもダントロレンは治療に有効なため長く用いられてきたが，MHの発症予防に対する効果は乏しいとされてきた．この研究により，ダントロレンはMHの発症予防の効果もある可能性を示唆する結論が得られた．
よって今後は，ダントロレンの予防的な臨床応用も視野に，MHの発症リスクの低減を図ることが可能になると期待される．
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