| Project/Area Number |
18K16519
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 敗血症 / AMPK / 骨格筋 / ＡＭＰＫ / 肝臓 / 臓器障害 |
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| Outline of Final Research Achievements |
Sepsis is a life-threatening organ damage caused by dysregulation of host biological responses to infection. We hypothesized that AMP-activated protein kinase (AMPK), which plays a central role in metabolism, plays a major role in the dysregulation of host biological responses. Skeletal muscle is a distinct but large organ from internal organs such as the liver and gastrointestinal tract. Skeletal muscle is also greatly involved in metabolism, and it has been reported that exercise improves the prognosis of mice after sepsis. We hypothesized that AMPK, which we have been studying, may be involved in this prognostic improvement. We overexpressed AMPK in skeletal muscle, and then checked the survival rate, systemic inflammatory response, and neutrophil infiltration of tissues in mice with reduced activity, but no significant differences were observed.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究で骨格筋にAMPKを過剰発現させ、活性を低下させたAMPK-DNマウスを使用した。AMPK-DNマウスでは盲腸結紮穿刺モデルによる敗血症後の生存率に有意差を認めなかった。全身の炎症反応や、組織の好中球浸潤を見ても、有意差を認めなかった。AMPKにはα、β、γのサブユニットを有し、AMPK-DNではαの活性は高率に低下させているがβやγの活性は残存しているといわれ、この活性の残存が完全にAMPKの活性を落とせていないことが原因と考えられた。
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