WEKO3
アイテム
Xa inhibitor edoxaban ameliorates hepatic ischemia-reperfusion injury via PAR-2-ERK 1/2 pathway
http://hdl.handle.net/10076/0002001563
http://hdl.handle.net/10076/0002001563b6ba368b-0cac-45e5-bd9b-60ac36a4969e
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2025DM0706.pdf (2.30 MB)
|
|
| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2025-07-31 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Xa inhibitor edoxaban ameliorates hepatic ischemia-reperfusion injury via PAR-2-ERK 1/2 pathway | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
前田, 光貴
× 前田, 光貴
|
|||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Hepatic ischemia-reperfusion injury causes liver damage during surgery. In hepatic ischemia-reperfusion injury, the blood coagulation cascade is activated, causing microcirculatory incompetence and cellular injury. Coagulation factor Xa (FXa)- protease-activated receptor (PAR)-2 signaling activates inflammatory reactions and the cytoprotective effect of FXa inhibitor in several organs. However, no studies have elucidated the significance of FXa inhibition on hepatic ischemia-reperfusion injury. The present study elucidated the treatment effect of an FXa inhibitor, edoxaban, on hepatic ischemia-reperfusion injury, focusing on FXa-PAR-2 signaling. A 60 min hepatic partial-warm ischemia-reperfusion injury mouse model and a hypoxia-reoxygenation model of hepatic sinusoidal endothelial cells were used. Ischemia-reperfusion injury mice and hepatic sinusoidal endothelial cells were treated and pretreated, respectively with or without edoxaban. They were incubated during hypoxia/reoxygenation in vitro. Cell signaling was evaluated using the PAR-2 knockdown model. In ischemia-reperfusion injury mice, edoxaban treatment significantly attenuated fibrin deposition in the sinusoids and liver histological damage and resulted in both anti-inflammatory and antiapoptotic effects. Hepatic ischemia-reperfusion injury upregulated PAR-2 generation and enhanced extracellular signal-regulated kinase 1/2 (ERK 1/2) activation; however, edoxaban treatment reduced PAR-2 generation and suppressed ERK 1/2 activation in vivo. In the hypoxia/reoxygenation model of sinusoidal endothelial cells, hypoxia/reoxygenation stress increased FXa generation and induced cytotoxic effects. Edoxaban protected sinusoidal endothelial cells from hypoxia/reoxygenation stress and reduced ERK 1/2 activation. PAR-2 knockdown in the sinusoidal endothelial cells ameliorated hypoxia/reoxygenation stress-induced cytotoxicity and suppressed ERK 1/2 phosphorylation. Thus, edoxaban ameliorated hepatic ischemia-reperfusion injury in mice by protecting against micro-thrombosis in sinusoids and suppressing FXa-PAR-2-induced inflammation in the sinusoidal endothelial cells. | |||||||||||
| 言語 | en | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文 / Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 19p | |||||||||||
| 書誌情報 |
発行日 2025-07-16 |
|||||||||||
| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1371/journal.pone.0292628 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| 値 | ミエダイガク | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2025-07-16 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第2332号 | |||||||||||
| 資源タイプ（三重大） | ||||||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||||||
