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非アルコール性脂肪性肝疾患モデルメダカの心筋病変に対する選択的PPARαモジュレーター、ナトリウム-グルコース共輸送体2阻害剤、スタチンの有効性の検討
http://hdl.handle.net/10191/0002001056
http://hdl.handle.net/10191/000200105620e065e5-dace-473d-8608-e77e942722a0
| 名前 / ファイル | ライセンス | アクション |
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本文 (2.66MB)
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要旨 (525KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2023-07-26 | |||||||||
| タイトル | ||||||||||
| タイトル | Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | 非アルコール性脂肪性肝疾患モデルメダカの心筋病変に対する選択的PPARαモジュレーター、ナトリウム-グルコース共輸送体2阻害剤、スタチンの有効性の検討 | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Nonalcoholic fatty liver disease | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Heart disease | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Medaka | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Selective peroxisome proliferator-activated | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | receptor alpha | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Sodium-glucose cotransporter 2 inhibitor | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Statin | |||||||||
| 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 | |||||||||
| 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 | |||||||||
| 著者 |
大越, 麻理奈
× 大越, 麻理奈
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. Methods: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis. Results: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4- and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy. Conclusion: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | Biochemical and Biophysical Research Communications. 2022, 625, 116-121. | |||||||||
| 言語 | en | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.1016/j.bbrc.2022.07.117 | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | © 2022 Elsevier Inc. All rights reserved. | |||||||||
| 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 | 13101 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 新潟大学 | |||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Niigata University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2023-03-23 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第5118号 | |||||||||
| 学位記番号 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 新大院博(医)第1109号 | |||||||||
| 言語 | ja | |||||||||
