Development of a novel animal model of hepatocellular carcinoma with nonalcoholic steatohepatitis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Keio University
• Principal Investigator: Aiura Koichi 慶應義塾大学, 医学部, 講師 (00184010)
• Co-Investigator(Kenkyū-buntansha): Itano Osamu 慶應義塾大学, 医学部, 講師 (90265827) ; Kitago Minoru 慶應義塾大学, 医学部, 講師 (70296599) ; Matsuda Sachiko 慶應義塾大学, 医学部, 特任講師 (90534537) ; Onishi Akira 日本大学, 生物資源科学部, 教授 (30414890)
• Co-Investigator(Renkei-kenkyūsha): Kojima Misaki 独立行政法人農業生物資源研究所, 家畜ゲノム研究ユニット, 上級研究員 (80355742) ; Tanigichi Yoshihito 杏林大学, 医学部, 教授 (00324616) ; Yoshiura Yasushi 独立行政法人水産総合研究センター, 増養殖研究所, 研究員 (90372052)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: NASHモデル / 動物モデル

Outline of Final Research Achievements

The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features.
Three-week-old C57BL/6J male mice were fed either a standard diet (MF) or a choline-deficient, high-fat diet (HFCD). The mice in the MF+diethylnitrosamine (DEN) and HFCD+DEN groups received a one-time intraperitoneal injection of DEN at the start of the respective feeding protocols. The mice in the HFCD and HFCD+DEN groups developed obesity early in the experiment and insulin resistance after 12 weeks. The HFCD+DEN group presented the highest incidence of nonalcoholic steatohepatitis. The levels of fibrosis and steatosis varied, but they tended to increase every 4 weeks in the HFCD and HFCD+DEN groups. Computed tomography scans indicated that all the HFCD+DEN mice developed hepatic tumors from 20 weeks, some of which were glutamine synthetase-positive.

Free Research Field

外科学