Activation of the AMPK/Nrf2 pathway ameliorates LPS-induced acute lung injury by inhibiting oxidative stress and reducing inflammation.

Background: Numerous diseases-related acute lung injury (ALI) contributed to high mortality. Currently, the therapeutic effect of ALI was still poor. The detailed mechanism of ALI remained elusive and this study aimed to elucidate the mechanism of ALI.

Method: This study was performed to expose the molecular mechanisms of AMPK/Nrf2 pathway regulating oxidative stress in LPS-induced AMI mice. The mouse ALI model was established via intraperitoneal injection of LPS, then the lung tissue and blood samples were obtained, followed by injection with Dimethyl fumarate (DMF). Finally, Western blot, HE staining, injury score, lung wet/dry ratio, reactive oxygen species (ROS) and ELISA were used to elucidate the mechanism of AMPK/Nrf2 pathway in LPS -induced acute lung injury by mediating oxidative stress.

Results: The lung tissue injury score was evaluated, showing higher scores in the model group compared to the AMPK activator and control groups. DCFH-DA indicated that LPS increased ROS production, while AMPK activator DMF reduced it, with the model group exhibiting higher ROS levels than the control and AMPK activator groups. The lung wet/dry ratio was also higher in the model group. Western blot analysis revealed LPS reduced AMPK and Nrf2 protein levels, but DMF reversed this effect. ELISA results showed elevated IL-6 and IL-1β levels in the model group compared to the AMPK activator and control groups.

Conclusion: CONCLUSION: Activating the AMPK/Nrf2 pathway can improve LPS-induced acute lung injury by down-regulation of the oxidative stress and corresponding inflammatory factor level.