Role of antioxidative transcription factor Nrf2 in strategies to protect against ischemia-reperfusion injury after lung transplantation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Fujita Health University (2016); Tohoku University (2014-2015)
• Principal Investigator: Hoshikawa Yasushi 藤田保健衛生大学, 医学部, 教授 (90333814)
• Co-Investigator(Renkei-kenkyūsha): TOGO Takeo 東北大学, 加齢医学研究所, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Nrf2活性化剤 / Nrf2標的遺伝子 / アポトーシス / 肺酸素化能 / Nrf2欠損ラット / 肺水腫

Outline of Final Research Achievements

To test whether Nrf2 protects lungs from ischemia-reperfusion injury after lung transplantation (LTx), wild-type (WT) rats underwent left LTx from Nrf2 knockout (KO) or WT rats, and pulmonary injury and edema were compared. Lung grafts from Nrf2 KO rats showed more pulmonary edema, reduced lung compliance, and less oxygenation when compared with grafts from WT rats. Pretreatment of the recipient rats with Nrf2 activator oltipraz attenuated ischemia-reperfusion-induced lung edema in the grafts from WT rats, but not in the grafts from Nrf2 KO rats. Oltipraz also induced enhanced expression of Nrf2 target genes, NAD(P)H quinone oxidoreductase 1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM) and reduced number of TUNEL positive cells in the grafts from WT rats. These results indicate that Nrf2 plays a role in protection against ischemia-reperfusion injury and that Nrf2 activators have a therapeutic potency for the prevention of primary graft dysfunction after LTx.

Free Research Field

呼吸器外科学