Basic research to prevent ventilator-induced organ failure targeting "regulated necrosis".

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16575
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Yokohama City University
• Principal Investigator: TAMADA Nao 横浜市立大学, 医学研究科, 客員研究員 (70439181)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ARDS / VILI / ネクローシス / アポトーシス

Outline of Final Research Achievements

The purpose of this study was to investigate whether artificial ventilation enhances the “regulated necrosis'' of alveolar epithelial cell death in ARDS and induces distant organ damage and dysfunction. Furthermore, the aim was to examine whether inhibitors targeting “regulated necrosis'' would suppress damage to the lungs and distant organs. High tidal volume ventilation induces apoptosis in alveolar epithelial cells in healthy lungs, but necrosis in alveolar epithelial cells in ARDS lungs. High tidal volume ventilation further promoted necrosis of alveolar epithelial cells and enhances lung injury than low tidal volume ventilation in ARDS lungs. However, high tidal volume ventilation did not further enhance “regulated necrosis.'' Therefore, we have been unable to examine whether inhibitors targeting “regulated necrosis'' suppress damage to the lungs and distant organs.

Free Research Field

救急医学・集中治療医学

Academic Significance and Societal Importance of the Research Achievements

ARDS肺において高容量換気が肺胞上皮細胞のネクローシスは進行させるものの，「制御されたネクローシス」の関与を証明できなかったため課題が残る結果となったが，別経路でネクローシスを進行させている可能性を見出した．