DSpace DSpace Softwareについて English
 

GINMU >
01 奈良県立医科大学 >
012 大学院 >
0122 学位請求論文 >
01221 博士論文(医学) >
2024年度 >

このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/10564/4449

タイトル: Tofogliflozin Delays Portal Hypertension and Hepatic Fibrosis by Inhibiting Sinusoidal Capillarization in Cirrhotic Rats
その他のタイトル: トホグリフロジンは肝硬変ラットにおける類洞毛細血管化を抑制することで門脈圧亢進症を抑制する
著者: Asada, Shohei
Kaji, Kosuke
Nishimura, Norihisa
Koizumi, Aritoshi
Matsuda, Takuya
Tanaka, Misako
Yorioka, Nobuyuki
Sato, Shinya
Kitagawa, Koh
Namisaki, Tadashi
Akahane, Takemi
Yoshiji, Hitoshi
キーワード: liver sinusoidal endothelial cell
hepatic stellate cell
sodium glucose transporter 2 inhibitors
oxidative stress
angiogenesis
発行日: 2024年3月19日火曜日
出版者: MDPI
引用: Cells. 2024 Mar, vol.13, no.6, article no.538
抄録: Background: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. Methods: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4 ) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. Results: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. Conclusions: Our study provides strong support for tofogliflozin in the prevention of liver cirrhosis-related PH.
内容記述: 権利情報:© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/10564/4449
ISSN: 2073-4409
DOI: https://doi.org/10.3390/cells13060538
学位授与番号: 24601甲第954号
学位授与年月日: 2025-03-14
学位名: 博士(医学)
学位授与機関: 奈良県立医科大学
出現コレクション:2024年度

このアイテムのファイル:

ファイル 記述 サイズフォーマット
02甲954本文の要旨.pdf02甲954本文の要旨110.85 kBAdobe PDF見る/開く
03甲954審査要旨.pdf03甲954審査要旨128.41 kBAdobe PDF見る/開く

このリポジトリに保管されているアイテムは、他に指定されている場合を除き、著作権により保護されています。

 

Valid XHTML 1.0! Powered by DSpace Software Copyright © 2002-2007 MIT and Hewlett-Packard - ご意見をお寄せください