Development of prevention methods for hepatitis C - related liver tumor focusing function of nuclear receptor PPAR

以核受体PPAR功能为重点的丙型肝炎相关肝脏肿瘤预防方法的开发

• 批准号: 22390060
• 负责人: AOYAMA Toshifumi
• 金额: $ 11.4万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390060/
• 关键词: 分子腫瘍学; C 型肝炎; 肝発癌; PPAR; アンタゴニスト; 中性脂肪; HCVコア蛋白; C型肝炎; HCC; 脂肪肝; コア蛋白; フィブレート; EPA; PPAR活性化; ミトコンドリア障害; フィブラート; 酸化ストレス

Presentation of hepatitis C virus - related liver tumor was found that activation of nuclear receptor: PPAR exerts as an essential factor. In this study, several attempts to prevent occurrence of liver tumor by means of PPAR antagonist (MK886) etc. were done, using transgenic mice expressing hepatitis C virus core protein. Administration of high dose MK886 (40 mg/kg/day) was confirmed to completely prevent occurrence of liver tumor, however, MK886 could cause fatal toxicity in some mice.

发现丙型肝炎病毒相关肝肿瘤的发生与核受体PPAR的激活有关。本研究利用表达丙型肝炎病毒核心蛋白的转基因小鼠，多次尝试利用PPAR拮抗剂（MK886）等预防肝脏肿瘤的发生。高剂量给药（40mg /kg/天）可完全预防肝脏肿瘤的发生，但在部分小鼠中可引起致死性毒性。

项目成果

PPARα is down-regulated following liver transplantation in mice.

小鼠肝移植后，PPARα下调。

• DOI: 10.1016/j.jhep.2011.08.021
• 发表时间: 2012-03
• 期刊: Journal of hepatology
• 影响因子: 25.7
• 作者: Nakagawa K;Tanaka N;Morita M;Sugioka A;Miyagawa S;Gonzalez FJ;Aoyama T
• 通讯作者: Aoyama T

Modulation of ammonium perfluorooctanoate-induced hepatic damage by genetically different PPARα in mice.

• DOI: 10.1007/s00204-011-0704-3
• 发表时间: 2012-01
• 期刊: Archives of toxicology
• 影响因子: 6.1
• 作者: Nakagawa T;Ramdhan DH;Tanaka N;Naito H;Tamada H;Ito Y;Li Y;Hayashi Y;Yamagishi N;Yanagiba Y;Aoyama T;Gonzalez FJ;Nakajima T
• 通讯作者: Nakajima T

目で見る解剖と生理・11巻消化系II

视觉解剖学和生理学第11卷消化系统II

• 发表时间: 2010
• 作者: 酒井規雄;藤原雅幸;他;Otsuka M;石井寛高,濱田知宏,佐久間康夫;青山俊文
• 通讯作者: 青山俊文

Attenuation of Kidney Injuries Maintains Serum Sulfatide Levels Dependent on Hepatic Synthetic Ability: A Possible Involvement of Oxidative Stress

• DOI: 10.1620/tjem.227.1
• 发表时间: 2012-05-01
• 期刊: TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 2.2
• 作者: Sheng, Xiaona;Nakajima, Takero;Hara, Atsushi
• 通讯作者: Hara, Atsushi

Down-regulation of SREBP-lc is associated with the development of bur ned-out NASH

SREBP-lc 的下调与烧坏 NASH 的发展相关

• 发表时间: 2010
• 期刊: J Hepatology
• 作者: Koyama M;Yin C;Ishii H;Sakuma Y,Kato M;青山俊文
• 通讯作者: 青山俊文