Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats

• Project/Area Number: 26462044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NINOMIYA Mizuki 九州大学, 医学研究院, 共同研究員 (30546461)
• Co-Investigator(Kenkyū-buntansha): 副島 雄二 九州大学, 医学研究院, 准教授 (30325526) ; 調 憲 群馬大学, 大学院医学系研究科, 教授 (70264025) ; 内山 秀昭 九州大学, 医学研究院, 共同研究員 (70380425) ; 吉住 朋晴 九州大学, 医学研究院, 准教授 (80363373) ; 池上 徹 九州大学, 大学病院, 助教 (80432938)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脂肪肝 / 虚血再灌流障害 / 温虚血再灌流障害 / 温阻血再灌流傷害

Outline of Final Research Achievements

Fatty liver rats underwent surgically induced partial hepatic ischemia followed by reperfusion. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers. Necrotic area and the concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), TNFα, and IL-6 were higher in fatty liver tissue than in normal liver tissue. The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2′-deoxyguanosine, TNFα, and IL-6. The protective effect of apocynin on fatty livers was greater than on normal livers.

Research Products

• [Journal Article] Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats (2016)
  • Author(s): Koichi Kimura, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Shinji Okano, Yoshihiko Maehara
  • Journal Title: Transplantation Volume: 100 Issue: 4 Pages: 791-800
  • DOI: 10.1097/tp.0000000000001130
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living donor liver transplantation (2015)
  • Author(s): M. Ninomiya, K. Shirabe, H. Kayashima, T. Ikegami, A. Nishie, N. Harimoto, Y. Yamashita, T. Yoshizumi, H. Uchiyama Y. Maehara
  • Journal Title: British Journal of Surgery Volume: in press Issue: 8 Pages: 944-951
  • DOI: 10.1002/bjs.9820
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 脂肪肝温阻血再灌流傷害におけるNADPH oxidaseシグナルの関与とその制御 (2016)
  • Author(s): 木村 光一, 調 憲, 岡部 弘尚, 伊藤 心二, 播本 憲史, 池上 徹, 内山 秀昭, 吉住 朋晴, 前原 喜彦
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-04-14
• [Presentation] 脂肪肝における温阻血再灌流傷害の増悪の分子機序解明と新しい治療の展開 (2015)
  • Author(s): 木村 光一, 調 憲, 吉田 佳弘, 今井 大祐, 王 歓林, 別城 悠樹, 松本 佳大, 武石 一樹, 伊藤 心二, 播本 憲史, 山下 洋市, 池上 徹, 岡野 慎士, 吉住 朋晴, 川中 博文, 前原 喜彦
  • Organizer: 第15回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-16 – 2015-04-18
• [Presentation] 脂肪肝における温阻血再灌流傷害の増悪の分子機序解明と新しい治療の展開 (2015)
  • Author(s): 木村 光一, 調 憲, 吉田 佳弘, 今井 大祐, 王 歓林, 別城 悠樹, 松本 佳大, 武石 一樹, 伊藤 心二, 播本 憲史, 山下 洋市, 池上 徹, 岡野 慎士, 吉住 朋晴, 川中 博文, 前原 喜彦
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-16