Role of the anti-oxidative transcription factor Nrf2 in ischemia-reperfusion injury after lung transplantation

DOI Open Access
  • Hoshikawa Yasushi
    Department of Thoracic Surgery, Fujita Health University School of Medicine

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  • 肺移植後虚血・再灌流肺障害予防戦略における抗酸化転写因子Nrf2の役割の解明

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Abstract

Lung transplantation (LTx) has become the mainstay for treatment of end-stage respiratory diseases. However postoperative 90-day mortality rate is 11% according to the international registry data and 5.4% in Japan. The most major cause of early death after LTx is primary graft dysfunction (PGD) mainly due to ischemia-reperfusion lung injury. Ischemia-reperfusion of the lung has been shown to induce overproduction of reactive oxygen species, which leads to the progression of severe lung injury and pulmonary edema. Nrf2 is a key transcription factor that activates many antioxidant enzymes. To test whether Nrf2 protects lungs from ischemia-reperfusion injury, 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 and reduced lung compliance when compared with those from WT rats. Pretreatment of the recipient rats with Nrf2 activator oltipraz attenuated ischemia-reperfusion-induced edema in the grafts from WT rats, but not in the grafts from Nrf2 KO 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 PGD after LTx.

Journal

  • Organ Biology

    Organ Biology 24 (2), 147-150, 2017

    The Japan Society for Organ Preservation and Biology

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