Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury

• Material Type: 博士論文
• Title: Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury
• Author/Editor: Ito, Takahiro
• Author Heading: Ito, Takahiro
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2018-03-26
• Publication Date (W3CDTF): 2018-03-26
• Alternative Title: 肝虚血再灌流障害におけるスフィンゴシン1リン酸受容体作動薬による類洞内皮保護について
• Degree grantor/type: 三重大学
• Date Granted: 2018-03-26
• Date Granted (W3CDTF): 2018-03-26
• Dissertation Number: 甲医学第1890号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第1890号
• Text Language Code: eng
• Alias of Author: イトウ, タカヒロ; 伊藤, 貴洋
• Subject Heading: Anti-inflammatory action; Endothelial stabilization; Sinusoidal blood flow; Vascular integrity; Vasorelaxation
• Target Audience: 一般
• Note (General): application/pdf; 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.; 本文 / Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine; 14p
• DOI: info:doi/10.1016/j.jss.2017.09.048; https://doi.org/info:doi/10.1016/j.jss.2017.09.048
• Persistent ID (NDL): info:ndljp/pid/11123712; https://dl.ndl.go.jp/pid/11123712
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-08-03T23:36:01+09:00
• Date Created (W3CDTF): 2018-07-19
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00017707; https://mie-u.repo.nii.ac.jp/records/12075
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2023-12-15 再収集