Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.

• 資料種別: 博士論文
• タイトル: Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.
• 著者・編者: Ozutsumi, Takahiro; Namisaki, Tadashi; Shimozato, Naotaka; Kaji, Kosuke; Tsuji, Yuki; Kaya, Daisuke; Fujinaga, Yukihisa; Furukawa, Masanori; Nakanishi, Keisuke; Sato, Shinya; Sawada, Yasuhiko; Saikawa, Soichiro; Kitagawa, Koh; Takaya, Hiroaki; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Noguchi, Ryuichi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 著者標目: Ozutsumi, Takahiro; Namisaki, Tadashi; Shimozato, Naotaka; Kaji, Kosuke; Tsuji, Yuki; Kaya, Daisuke; Fujinaga, Yukihisa; Furukawa, Masanori; Nakanishi, Keisuke; Sato, Shinya; Sawada, Yasuhiko; Saikawa, Soichiro; Kitagawa, Koh; Takaya, Hiroaki; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Noguchi, Ryuichi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2020-03-21
• 出版年（W3CDTF）: 2020-03-21
• 並列タイトル等: エスジーエルティー2阻害薬（カナグリフロジン）およびジペプチジルペプチダーゼ４阻害薬（テネリグリプチン）との併用療法は非糖尿病ラットモデルにおける非アルコール性脂肪肝炎の進行を抑制する
• タイトル（掲載誌）: International journal of molecular sciences
• 巻号年月日等（掲載誌）: 21 6
• 掲載巻: 21
• 掲載号: 6
• 掲載ページ: Article No.2164-
• ISSN（掲載誌）: ISSN : 1422-0067
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2021-03-15
• 報告番号: 甲第765号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: non-alcoholic steatohepatitis; hepatic fibrogenesis; hepatocarcinogenesis; canagliflozin; teneligliptin
• 対象利用者: 一般
• 一般注記: type:Thesis; Hepatocellular carcinoma (HCC) is the strongest independent predictor of mortality in non-alcoholic steatohepatitis (NASH)-related cirrhosis. The effects and mechanisms of combination of sodium-dependent glucose cotransporter inhibitor and canagliflozin (CA) and dipeptidyl peptidase-4 inhibitor and teneligliptin (TE) on non-diabetic NASH progression were examined. CA and TE suppressed choline-deficient, L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. CA alone or with TE significantly decreased proinflammatory cytokine expression. CA and TE significantly attenuated hepatic lipid peroxidation. In vitro studies showed that TE alone or with CA inhibited cell proliferation and TGF-β1 and α1 (I)-procollagen mRNA expression in Ac-HSCs. CA+TE inhibited liver fibrogenesis by attenuating hepatic lipid peroxidation and inflammation and by inhibiting Ac-HSC proliferation with concomitant attenuation of hepatic lipid peroxidation. Moreover, CA+TE suppressed in vivo angiogenesis and oxidative DNA damage. CA or CA+TE inhibited HCC cells and human umbilical vein endothelial cell (HUVEC) proliferation. CA+TE suppressed vascular endothelial growth factor expression and promoted increased E-cadherin expression in HUVECs. CA+TE potentially exerts synergistic effects on hepatocarcinogenesis prevention by suppressing HCC cell proliferation and angiogenesis and concomitantly reducing oxidative stress and by inhibiting angiogenesis with attenuation of oxidative stress. CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH.; 博士（医学）・甲第765号・令和3年3月15日; © 2020 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 (http://creativecommons.org/licenses/by/4.0/).; identifier:International journal of molecular sciences Vol.21 No.6 Article No.2164 (2020 Mar); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3889; identifier:International journal of molecular sciences, 21(6): Article No.2164
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.3390/ijms21062164
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

目次

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/1/01%e7%94%b2765%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/2/02%e7%94%b2765%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/3/02%e7%94%b2765%e6%9c%ac%e6%96%87.pdf fulltext