Role of the anti-oxidative transcription factor Nrf2 in ischemia-reperfusion injury after lung transplantation
Role of the anti-oxidative transcription factor Nrf2 in ischemia-reperfusion injury after lung transplantation
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抗氧化转录因子Nrf2在肺移植后缺血再灌注损伤中的作用
DOI：
10.11378/organbio.24.147
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
星川 康
中科院分区：
文献类型：
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作者：
星川 康
肺移植（LTx）已成为治疗终末期呼吸系统疾病的主要手段。然而，根据国际登记数据，术后90天死亡率为11%，日本为5.4%。LTx后早期死亡的最主要原因是主要由于缺血-再灌注肺损伤引起的原发性移植物功能障碍（PGD）。肺的缺血再灌注已显示诱导活性氧的过度产生，这导致严重肺损伤和肺水肿的进展。nrf 2是一个关键的转录因子，激活许多抗氧化酶。为了测试Nrf 2是否保护肺免受缺血-再灌注损伤，野生型（WT）大鼠经历来自Nrf 2敲除（KO）或WT大鼠的左LTx，并比较肺损伤和水肿。与WT大鼠相比，Nrf 2 KO大鼠的肺移植物显示出更多的肺水肿和肺顺应性降低。用Nrf 2激活剂oltipraz预处理受体大鼠可减轻WT大鼠移植物中缺血再灌注诱导的水肿，但Nrf 2 KO大鼠移植物中无此作用。这些结果表明，Nrf 2在防止缺血-再灌注损伤中起作用，并且Nrf 2激活剂具有预防LTx后PGD的治疗效力。
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.