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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 >
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http://hdl.handle.net/10564/4449
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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
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