Nrf2 Activation Protects Against ALI/ARDS By Regulating Macrophage Polarization

Objective: The incidence and mortality of ALI/ARDS is high currently,however,no effective strategies have been proved.This study aims to explore the protection and the underlying mechanism of Nrf2 activation on ALI/ARDS.Methods: Mouse ALI/ARDS model was established by intratracheal or intraperitoneal LPS.Mice survivals,inflammatory gene expression in lung and serum cytokine level were studied to confirm the protection of intraperitoneal tBHQ induced Nrf2 activation on ALI/ARDS and the possible pathway.In vitro,peritoneal macrophages were treated with different stimulus to explore how Nrf2 activation could influence macrophage polarization and WB,RT-QPCR and siRNA were applied.Results: Intraperitoneal tBHQ injection significantly reduced the mortality of both ALI/ARDS and septic mice within 7 days,attenuated pathologic injury of lung,inhibited IL6 and TNF? gene expression in lung tissue and their cytokine level in serum but promoted IL10,mainly in acute early phase.In vitro experiments indicated that Nrf2 activation could promote macrophage polarization toward M2,however,inhibit LPS/IFN?induced M1 polarization.Conclusions: Nrf2 activation could reduce the mortality of ALI/ARDS mice and attenuate lung injury through mediating M1/M2 macrophage polarization balance mainly in early phase of acute lung injury.