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.
| Project/Area Number |
16K19885
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
Shimada Shingo 北海道大学, 医学研究院, 特任助教 (40755576)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脂肪肝 / 肝癌 / 虚血再灌流障害 / 抗酸化 / 脂肪酸 / IMS / 虚血再灌流 / リゾリン脂質 / 肝切除 / 肝細胞癌 / 肝癌細胞 / 質量分析イメージング / ラット / 水素 / NaHS / 線維化 / MALDI / 質量分析 / 肝障害 / 発癌 / 抗炎症 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(9 results)
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[Presentation] Elucidation of the role of lyso-phospholipids on hepatic warm ischemia and reperfusion injury; Comprehenive analysis by imaging mass spectrometry2019
Author(s)
Kengo Shibata, Takahiro Hayasaka, Moto Fukai, Koichi Kato, Takahisa Ishikawa, Kohei Umemoto, Shingo Shimada, Nozomi Kobayashi, Tsuyoshi Shimamura, Taichi Kimura, and Akinobu Taketomi
Organizer
19th Congress of the European Society for Organ Transplantation (ESOT 2019). Copenhagen, Denmak
Related Report
Int'l Joint Research
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[Presentation] Elucidation of the mechanisms of hepatic warm ischemia and reperfusion injury in rats; Exploration of predictive markers of IRI by imaging mass spectrometry.2019
Author(s)
Kengo Shibata, Takahiro Hayasaka, Moto Fukai, Koichi Kato, Takahisa Ishikawa, Kohei Umemoto, Shingo Shimada, Nozomi Kobayashi, Tsuyoshi Shimamura, Taichi Kimura, and Akinobu Taketomi
Organizer
16th Congress of the Asian Society of Transplantation (CAST 2019). Greator Noida, India
Related Report
Int'l Joint Research
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[Presentation] 虚血再灌流傷害に対する水素ガスの作用点の探索2019
Author(s)
深井原, 柴田賢吾, 坂本聡大, 島田慎吾, 小林希, 石川隆壽, 若山顕治, 藤好真人, 川村典生, 嶋村剛, 武冨紹信
Organizer
第46回 日本臓器保存生物医学会学術集会 (福島,ふくしま医療機器開発支援センター)
Related Report
Invited
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[Presentation] 生存シグナル増強を目指した機械灌流による肝グラフトの薬剤性コンディショニング法の探索2019
Author(s)
深井原、柴田賢吾, 島田慎吾, 石川隆壽, 若山顕治, 藤好直, 小林希, 加藤紘一, 早坂孝宏, 三野和宏, 川村典生, 嶋村剛，武冨紹信
Organizer
第119回日本外科学会定期学術集会, 大阪国際会議場
Related Report
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