Development of novel treatment strategy against ischemia reperfusion lung injury after lung transplantation via the inhibition of necroptosis.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Osaka University
• Principal Investigator: Kanou Takashi 大阪大学, 医学系研究科, 助教 (70528455)
• Co-Investigator(Kenkyū-buntansha): 南 正人 大阪大学, 医学部附属病院, 特任教授(常勤) (10240847) ; 大瀬 尚子 大阪大学, 医学系研究科, 助教 (10570559) ; 舟木 壮一郎 大阪大学, 医学系研究科, 准教授 (50464251) ; 新谷 康 大阪大学, 医学系研究科, 教授 (90572983)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺移植

Outline of Final Research Achievements

Our research was conducted with the goal of developing a new treatment for ischemia-reperfusion lung injury after lung transplantation, targeting cell death, especially necroptosis. After establishing a rat lung transplantation model and testing multiple drug candidates, it was found that the calpain inhibitor ALLN significantly suppressed ischemia-reperfusion lung injury associated with long-term ischemia and necroptosis. Pathological and biochemical analyzes were performed, and it was considered that the above effects were exhibited by suppressing the signal pathway of necroptosis. The analyses are proceeding smoothly, and we are in the process of preparing for future academic activities and thesis presentation.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

肺移植実施症例数は年々増加しており、また移植を必要とする患者数も増加の一途である。一方、肺移植後の治療成績は他の臓器移植と比較して、いまだ不良である。特に急性期合併症に対する対策の確立が急務である。今回、カルパイン阻害薬を臓器の灌流保存液に添加することで肺移植後の虚血再灌流肺傷害を立証しえた。この結果にもとづき、細胞死を標的とした肺移植後の急性期合併症の予防法を確立することが本研究の学術的社会的意義と考える。