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Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury
http://hdl.handle.net/10076/00017707
http://hdl.handle.net/10076/00017707cf9f0340-6cdd-4276-8935-57e58c86e6e3
名前 / ファイル | ライセンス | アクション |
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2017DM033 (5.0 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2018-07-19 | |||||||||||
タイトル | ||||||||||||
タイトル | Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury | |||||||||||
言語 | en | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Anti-inflammatory action | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Endothelial stabilization | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Sinusoidal blood flow | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Vascular integrity | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Vasorelaxation | |||||||||||
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 |
伊藤, 貴洋
× 伊藤, 貴洋
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抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | BACKGROUND: Functional and structural damages in sinusoidal endothelial cells (SECs) have a crucial role during hepatic ischemia-reperfusion injury (IRI). In regulating endothelial function, sphingosine-1-phosphate receptor 1 (S1PR1), which is a G protein-coupled receptor, has an important role. The present study aimed to clarify whether SEW2871, a selective S1PR1 agonist, can attenuate hepatic damage caused by hepatic IRI, focusing on SEC functions.METHODS: In vivo, using a 60-min partial-warm IRI model, mice were treated with SEW2871 or without it (with vehicle). In vitro, isolated SECs pretreated with SEW2871 or without it (with vehicle) were incubated with hydrogen peroxide.RESULTS: Compared with the IRI + vehicle group, SEW2871 administration significantly improved serum transaminase levels and liver damage, attenuated infiltration of Ly-6G and mouse macrophage antigen-1-positive cells, suppressed the expression of vascular cell adhesion molecule-1 and proinflammatory cytokines in the liver, and enhanced the expressions of endothelial nitric oxide synthase (eNOS) and vascular endothelial (VE) cadherin in the liver (eNOS/β-actin [median]: 0.24 versus 0.53, P = 0.008; VE-cadherin/β-actin [median]: 0.21 versus 0.94, P = 0.008). In vitro, compared with the vehicle group, pretreatment of SECs with SEW2871 significantly increased the expressions of eNOS and VE-cadherin (eNOS/β-actin [median]: 0.22 versus 0.29, P = 0.008; VE-cadherin/β-actin [median]: 0.38 versus 0.67, P = 0.008). As results of investigation of prosurvival signals, SEW2871 significantly increased Akt phosphorylation in SECs and decreased lactate dehydrogenase levels in supernatants of SECs.CONCLUSIONS: These results indicate that S1PR1 agonist induces attenuation of hepatic IRI, which might be provided by preventing SEC damage. S1PR1 may be a therapeutic target for the prevention of early sinusoidal injury after hepatic IRI. | |||||||||||
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 | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | 14p | |||||||||||
書誌情報 |
発行日 2018-03-26 |
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DOI | ||||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | 10.1016/j.jss.2017.09.048 | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
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出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
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 | 2018-03-26 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 甲医学第1890号 | |||||||||||
ノート | ||||||||||||
値 | Journal of Surgical Research 2018 Feb;222:139-152, ISSN:0022-4804 に掲載 | |||||||||||
資源タイプ(三重大) | ||||||||||||
値 | Doctoral Dissertation / 博士論文 |