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Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat
http://hdl.handle.net/2237/16803
http://hdl.handle.net/2237/16803bcc6c81e-8fa4-4262-b0e3-ff6b7d005fce
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
k9756.pdf (2.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-10-01 | |||||
| タイトル | ||||||
| タイトル | Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat | |||||
| 言語 | en | |||||
| 著者 |
Moriya, Takashi
× Moriya, Takashi× Kitamori, Kazuya× Naito, Hisao× Yanagiba, Yukie× Ito, Yuki× Yamagishi, Nozomi× Tamada, Hazuki× Jia, Xiaofang× Tsuchikura, Satoru× Ikeda, Katsumi× Yamori, Yukio× Nakajima, Tamie |
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| 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 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | The final publication is available at www.springerlink.com | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Steatohepatitis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Inflammation | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | TNF-α | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | NF-κb | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Fibrosis | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: The aim of this study was to identify the molecular mechanisms underlying high-fat and high-cholesterol (HFC) diet-induced steatohepatitis and associated liver fibrosis progression in a novel stroke-prone, spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rat model. Methods: SHRSP5/Dmcr rats were given the control or HFC-diet for 2, 8, and 16 weeks. Plasma and hepatic gene expression of key molecules involved in fatty acid oxidation, inflammation, oxidative stress, and fibrosis were subsequently analyzed. Results: Rats fed the HFC-diet showed increased plasma tumor necrosis factor-α (TNF-α) and hepatic p50/p65 signals, but reduced hepatic Cu2+/Zn2+-superoxide dismutase across the treatment period and reduced plasma total adiponectin at 8 weeks. In HFC-diet-fed rats, transforming growth factor-β1 (TGF-β1) was elevated prior to the appearance of obvious liver fibrosis pathology at 2 weeks, followed by elevations in platelet-derived growth factor-B (PDGF-B) and α-smooth muscle actin (α-SMA), corresponding to evident liver fibrosis, at 8 weeks and by α1 type I collagen production at 16 weeks. The HFC-diet increased hepatic total cholesterol accumulation, although hepatic triglyceride declined by 0.3-fold from 2 to 16 weeks due to reduced hepatic triglyceride synthesis, as suggested by the diacylglycerol acyltransferase 1 and 2 measurements. Conclusions: TNF-α and p50/p65 molecular signals appeared to be major factors for HFC-diet-induced hepatic inflammation and oxidative stress facilitating liver disease progression. While the up-regulation of TGF-β1 prior to the appearance of any evident liver fibrosis could be an early signal for progressive liver fibrosis, elevated PDGF-B and α-SMA levels signified evident liver fibrosis at 8 weeks, and subsequent increased α1 type I collagen production and reduced triglyceride synthesis indicated extensive liver fibrosis at 16 weeks in this novel SHRSP5/Dmcr model. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成24年4月27日 森谷隆氏の博士論文として提出された | |||||
| 言語 | ja | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | First published online: 2012-03-10 | |||||
| 言語 | en | |||||
| 出版者 | ||||||
| 出版者 | Springer | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 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 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1007/s12199-012-0273-y | |||||
| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 1342-078X | |||||
| 書誌情報 |
en : Environmental Health and Preventive Medicine 巻 17, 号 6, p. 444-456, 発行日 2012-11 |
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| 学位名 | ||||||
| 言語 | ja | |||||
| 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 | 13901 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 名古屋大学 | |||||
| 言語 | en | |||||
| 学位授与機関名 | Nagoya University | |||||
| 学位授与年度 | ||||||
| 値 | 2012 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2012-11-01 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第9756号 | |||||
| 著者版フラグ | ||||||
| 値 | publisher | |||||
| URI | ||||||
| 識別子 | http://dx.doi.org/10.1007/s12199-012-0273-y | |||||
| 識別子タイプ | DOI | |||||
| URI | ||||||
| 識別子 | http://hdl.handle.net/2237/16803 | |||||
| 識別子タイプ | HDL | |||||
