Is AMP-activating enzyme in skeletal muscle associated with sepsis prognosis?

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K16519
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Ehime University
• Principal Investigator: Kikuchi Satoshi 愛媛大学, 医学系研究科, 准教授 (00467854)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 敗血症 / AMPK

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.

Free Research Field

敗血症

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。