Hydrogen inhalation inhibits skeletal muscle damage and ectopic adipocyte accumulation after hindlimb ischemia/reperfusion injury in mice

Research Project

Project/Area Number	18K16401
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Keio University
Principal Investigator	Hayashi Masanori 慶應義塾大学, 医学部(信濃町), 助教 (20793475)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	下肢虚血再灌流 / 水素ガス / 水素 / 下肢虚血再灌流障害 / 虚血再灌流 / 虚血再灌流障害 / 下肢動脈閉塞
Outline of Final Research Achievements	A new mouse model of lower limb ischemia-reperfusion was created in which the left hind lower limb of mice was ischemia-conditioned with a bandage. The effect of hydrogen gas on the model was verified by comparing a group that received hydrogen gas with a control group that received air. Hydrogen gas administration significantly suppressed myocyte necrosis. In the control group, after myocyte necrosis was caused by ischemia, regenerated myocytes and some of them were replaced by adipocytes, but in the hydrogen gas group, most of the normal myocytes were maintained and the appearance of adipocytes was also suppressed. In addition, the infiltration of neutrophils, lymphocytes, and macrophages into inflammatory cells was significantly inhibited, as was IL-6, a proinflammatory cytokine.
Academic Significance and Societal Importance of the Research Achievements	急性下肢動脈閉塞は致死率の高い疾患であるが、致死率の高い原因の一つに、血行再建後の虚血再還流障害があげられる。今回の研究により、下肢虚血再灌流に対して水素ガスを吸引することで炎症が抑制される可能性を示した。実臨床においても、急性下肢動脈閉塞の患者様に水素ガスを吸引させることで、血行再建後の虚血再還流障害を抑制できる可能性が示唆された。