| Project/Area Number |
15KK0131
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Sports science
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Research Collaborator |
Powers Scott K University of Florida, Department of Applied Physiology and Kinesiology, 教授
Smuder Ashley J University of Florida, Department of Applied Physiology and Kinesiology, 助教
Naito Hisashi
Yoshihara Toshinori
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| Project Period (FY) |
2016 – 2018
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
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| Keywords | 筋萎縮 / 横隔膜 / ミトコンドリア / 機械的人工換気 / 硫化物 |
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| Outline of Final Research Achievements |
We investigated the hypothesis that H2S preconditioning will protect the diaphragm against ventilator-induced diaphragm dysfunction (VIDD). Rats were randomly assigned to one of four groups: 1) 12 h spontaneous breathing (SB) with saline (SB-SALINE); 2) SB with Na2S as a H2S donor (SB-H2S); 3) 12 h of mechanical ventilation (MV) with saline (MV-SALINE); 4) MV with Na2S (MV-H2S). Compared to both SB-SALINE and SB-H2S, MV resulted in significant diaphragm atrophy and contractile dysfunction. Importantly, treatment with Na2S prior to MV protected the diaphragm against VIDD. Further, 12 h of MV resulted in increased mitochondrial uncoupling as evidenced by a significant decrease in the mitochondrial respiratory control ratio in mitochondria isolated from the diaphragm of MV-SALINE animals. Importantly treatment with H2S protected diaphragmatic mitochondria against MV-induced uncoupling. Our findings support the hypothesis that H2S preconditioning protects the diaphragm against VIDD.
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| Academic Significance and Societal Importance of the Research Achievements |
主な呼吸筋である横隔膜は，人工呼吸器の装着などにより自発的な収縮を軽減すると，わずか半日で急激な萎縮と機能不全を示す．呼吸筋の機能低下は易疲労感や生活活動量の低下をもたらすことから，横隔膜の機能を維持/回復する方法の開発が課題となっている．本研究では，心筋や下肢骨格筋においてミトコンドリア機能を保護する可能性が示されている硫化物の投与が，横隔膜機能不全へ及ぼす影響を明らかにすることを目的とした．その結果，人工呼吸器使用直前の単回投与により，横隔膜萎縮および機能不全が抑制されることを示した．本研究の成果は，横隔膜機能保護の新たな取り組みにつながることが期待できる．
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