A basic research to elucidate the mechanism of preconditioning against ischemia-reperfusion injury and its therapy

• Project/Area Number: 26462368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: International University of Health and Welfare (2016); Yokohama City University (2014-2015)
• Principal Investigator: Kurahashi Kiyoyasu 国際医療福祉大学, 大学病院, 教授 (50234539)
• Co-Investigator(Kenkyū-buntansha): 矢澤 卓也 獨協医科大学, 医学部, 教授 (50251054) ; 馬場 靖子 横浜市立大学, 附属市民総合医療センター, 講師 (80453041)
• Co-Investigator(Renkei-kenkyūsha): SAITO Izumu 東京大学, 医科学研究所, 教授 (70158913)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ARDS / 再灌流傷害 / HIF / 低酸素 / アポトーシス / 再灌流障害 / 肺傷害 / 虚血再灌流障害 / 転写因子 / サイトカイン / 虚血

Outline of Final Research Achievements

Ischemia occurs in accordance with hypoxia. It is well known that hypoxia-inducible factor (HIF)-1 expresses in hypoxic tissue and has an anti-inflammatory property. Acute respiratory distress syndrome (ARDS), a major cause of hypoxia, causes apoptosis through Fas/FasL pathway. Dimethyloxalylglycine (DMOG), a prolyl hydroxylase domain protein (PHD) inhibitor, suppresses Fas and thus diminishes apoptosis, which preserves the alveolar barrier function. Anti-apoptotic effects of DMOG and the suppression of Fas effects were not observed when HIF-1 pathway was inhibited by some ways such as siRNA. These findings suggest that anti-apoptotic effects of DMOG are dependent of HIF-1.

Research Products

• [Journal Article] Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-Induced Apoptosis and Lung Injury in Mice. (2016)
  • Author(s): Nagamine Y, Tojo K, Yazawa T, Takaki S, Baba Y, Goto T, Kurahashi K
  • Journal Title: Am J Respir Cell Mol Biol Volume: 55 Pages: 878-888
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effects of continuous positive airway pressure on a nonventilated lung during one-lung ventilation: A prospective laboratory study in rats. (2016)
  • Author(s): Tojo K, Goto T, Kurahashi K.
  • Journal Title: Eur J Anaesthesiol. Volume: 33 Issue: 10 Pages: 776-83
  • DOI: 10.1097/eja.0000000000000460
  • Peer Reviewed / Open Access
• [Journal Article] Adrenaline aggravates lung injury caused by liver ischemia-reperfusion and high-tidal-volume ventilation in rats. (2016)
  • Author(s): Ota S, Yazawa T, Tojo K, Baba Y, Uchiyama M, Goto T, Kurahashi K.
  • Journal Title: J Intensive Care Volume: 4 Issue: 1 Pages: 8-8
  • DOI: 10.1186/s40560-016-0130-y
  • Peer Reviewed
• [Journal Article] Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats. (2015)
  • Author(s): Tojo K, Nagamine Y, Yazawa T, Mihara T, Baba Y, Ota S, Goto T, Kurahashi K.
  • Journal Title: Intensive Care Med Exp. Volume: 3 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s40635-015-0056-z
  • Peer Reviewed
• [Journal Article] 肺保護換気が必要な手術・麻酔 (2015)
  • Author(s): 倉橋 清泰
  • Journal Title: 日本臨床麻酔学会誌 Volume: 35 Pages: 337-343
  • NAID: 130005094079
• [Presentation] Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-induced Apoptosis and Lung Injury in Mice. (2016)
  • Author(s): Nagamine Y, Tojo K, Yazawa T, Takaki S, Baba Y, Goto T, Kurahashi K
  • Organizer: American Thoracic Society International Conference 2016
  • Place of Presentation: San Francisco, California
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Dimethyloxalylglycine, a prolyl hydroxylase inhibitor, attenuates Fas ligand-induced apoptosis and lung injury in mice. (2016)
  • Author(s): Yusuke Nagamine, Kentaro Tojo, Takuya Yazawa, Shunsuke Takaki, Yasuko Baba, Takahisa Goto, Kiyoyasu Kurahashi
  • Organizer: 第56回 日本呼吸器学会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] 腹臥位換気 (2016)
  • Author(s): 倉橋 清泰
  • Organizer: 第43回日本集中治療医学会学術集会
  • Place of Presentation: 兵庫
  • Year and Date: 2016-02-11
  • Invited
• [Presentation] LUNG-SAFE study: 急性呼吸窮迫症候群に関する 大規模多施設共同前向き観察研究 (2015)
  • Author(s): 倉橋 清泰, John Laffey, Giacomo Bellani, Tai Pham, Eddy Fan
  • Organizer: 第37回日本呼吸療法医学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-07-17
• [Presentation] Prolyl hydroxylase阻害薬であるDimethloxalylglycine（DMOG）は，マウスのFas-Fas ligand系アポトーシスによる肺傷害を軽減する (2015)
  • Author(s): 長嶺祐介，東條健太郎，高木俊介，馬場靖子，後藤隆久，倉橋清泰
  • Organizer: 日本麻酔科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-28 – 2015-05-30
• [Presentation] Prolyl hydroxylase阻害薬であるDimethloxalylglycine（DMOG）は，マウスのFas-Fas ligand系アポトーシスによる肺傷害を軽減する (2015)
  • Author(s): 長嶺祐介，東條健太郎，高木俊介，馬場靖子，後藤隆久，倉橋清泰
  • Organizer: 日本麻酔科学会第62回学術集会
  • Place of Presentation: 兵庫
  • Year and Date: 2015-05-28
• [Presentation] Proryl hydroxylase 阻害薬であるDimethloxalylglycine （DMOG）は，肺胞上皮細胞株MLE15のFas-Fas ligand系によるアポトーシスを抑制する (2015)
  • Author(s): 長嶺祐介，東條健太郎，倉橋清泰
  • Organizer: 第22回バイオフィジオロジー研究会
  • Place of Presentation: 京都
  • Year and Date: 2015-02-20 – 2015-02-21