Elucidation of molecular pathology and development of a method for overcoming susceptibility to disabilities and metastasis by enhancing antioxidant capacity after hepatectomy for fatty liver.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19885
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Hokkaido University
• Principal Investigator: Shimada Shingo 北海道大学, 医学研究院, 特任助教 (40755576)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脂肪肝 / 肝癌 / 虚血再灌流障害 / 抗酸化 / 脂肪酸 / IMS

Outline of Final Research Achievements

We established a comprehensive analysis method of lipids and fatty acids in the liver tissue using rat fatty liver, animal model for liver ischemia-reperfusion, 70% hepatectomy, and mass spectrometry imaging (IMS). Mimicking the fatty liver microenvironment, hepatoma cell lines were cultured in the presence of oleic acid / palmitic acid, and proliferation, changes in malignancy, etc. were evaluated by molecular biology and lipid / fatty acid analysis. During warm ischemia-reperfusion, Lysophosphatidylinositol (LPI) and bile acids accumulated in the hepatic tissue Zone 1 in an ischemic time-dependent manner during ischemia, and this tendency was enhanced in fatty liver. LPI administration rapidly increased the cytosolic Ca2 + concentration in hepatocyte and stellate cell lines.

Free Research Field

肝臓外科

Academic Significance and Societal Importance of the Research Achievements

脂肪肝では軽度の持続的障害により抗酸化酵素、脂肪酸代謝酵素の発現が低下しており、虚血再灌流や肝切除後に障害を受け易いため、これらを軽減する方法の確立が望まれる。LPIとその特異的受容体 (GPR55) が肝虚血再灌流、肝切除後の傷害、再生、癌細胞発育に与える影響を、種々の阻害剤、賦活剤を用いて検討中であるが、これらの検討は、肝癌細胞の微小環境におけるリゾリン脂質、脂肪酸の役割に焦点をあてる新たな試みであり、新たな細胞間相互作用の発見と治療法開発の基礎的知見になるはずである。