2023 Fiscal Year Final Research Report
New approach for the mechanisms of septic encephalopathy based on cyclophilin D signal transduction and mitochondrial permeabilty transition pore structure
| Project/Area Number |
20K09255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石田 裕介 東京医科大学, 医学部, 講師 (40805884)
柴田 勝一郎 東京医科大学, 医学部, 助教 (70869429)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 敗血症性脳症 / シクロフィリンＤ / ミトコンドリア / アポトーシス / オートファジー / マイトファジー |
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| Outline of Final Research Achievements |
In this study, we attempted to comprehensively analyze the actual status of septic encephalopathy (SAE) in 2020 by Protein Array analysis of the role of CypD signaling pathway in cell death and apoptosis execution pathway. Chemokines increased 6 and 18 hours after CLP creation. In brain GSH/Nrf2 analysis, significant changes in HO-1 were observed at 18 hours after CLP preparation. 2021-2023, mitophagy analysis was performed, but the immunostaining of the samples for scanning electron microscopy was not sufficient for adequate analysis. Cryo-EM analysis could not be performed in this study.
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| Free Research Field |
麻酔・蘇生学
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| Academic Significance and Societal Importance of the Research Achievements |
敗血症関連脳症（Sepsis associated encephalopathy; SAE）の脳障害発症機序は未だに機序や責任分子も明らかではない。本成果は十分に得られなかったが、研究では、SAEの実態を脳内ケモカインの役割やMPT誘発ミトコンドリア機能不全の中心的役割を担うミトコンドリア内のCyclophilin D（CypD）と脳内抗酸化ストレス機構のGSH/Nrf2を機軸とした情報伝達系が関与することを見出せた。SAEの機序解明、新規防御法開発、麻酔科学・蘇生学・神経集中治療学領域での安全性と信頼性を高めることを目指すことに繋がったものと考える。
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