Quantitative diagnosis of non-alcoholic steatohepatitis by ultrasound and elucidation of the mechanism of occurrence by ultratrace mass spectrometry

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K12119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90130:Medical systems-related
• Research Institution: Doshisha University
• Principal Investigator: WATANABE Yoshiaki 同志社大学, 研究開発推進機構, 嘱託研究員 (60148377)
• Co-Investigator(Kenkyū-buntansha): 秋山 いわき 同志社大学, 生命医科学部, 教授 (80192912) ; 池川 雅哉 同志社大学, 生命医科学部, 教授 (60381943) ; 飯島 尋子 兵庫医科大学, 医学部, 教授 (80289066) ; 吉田 憲司 千葉大学, フロンティア医工学センター, 准教授 (10572985)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: NASH / 胆汁酸 / メダカ / 腸肝循環 / イメージング質量分析 / 超音波

Outline of Final Research Achievements

A new system to elucidate the pathogenic basis of non-alcoholic hepatitis from the metabolic aspect in detail using a medaka model is developed. Specifically, the main bile acid of medaka, which is rare for fish, is C24 (TCA) and C27 (THCA), and succeeded in visualizing the distribution of these two bile acids within one medaka individual. In addition, the main component analysis revealed the site and metabolism of each digestive organ. Regarding the relationship It was suggested that these two bile acids are functioning. Using this research method, it will be possible to comprehensively analyze the enterohepatic circulation of bile including bile acids, which will lead to the elucidation of the molecular basis from fatty liver to carcinogenesis in the model of one individual medaka.

Free Research Field

超音波エレクトロニクス

Academic Significance and Societal Importance of the Research Achievements

肝がん（HCC）への進行性が注目されている非アルコール性脂肪性肝（NASH）の発生機序の解明を胆汁酸の分布に着目し，メダカを対象種として実験的な検討を行った．メダカ成魚の一個体全体に対して12μm厚の全身凍結切片を作製し，消化器系における顕微質量計を用いてイメージング質量分析を行い，肝臓・胆嚢・上部～下部腸官領域で得られたスペクトラムの特徴を多変量解析や機械学習法を応用した画像統計ソフトを用いて特定した．この結果，胆汁酸の腸肝循環の解明がNASHの発生機序解明に繋がる可能性が示唆された．