Sevoflurane enhances autophagy via Rac1 to attenuate lung ischaemia‒reperfusion injury.

ABSTRACT

Sevoflurane can attenuate lung ischaemia‒reperfusion injury (LIRI). However, the protective mechanism is unclear. In this study, we developed a LIRI model in vivo that animals (SD, n = 15) were subjected to the administration of 2.2 % sevoflurane 30 min before the onset of left pulmonary artery clamping for 45 min, which was then followed by 60 min of reperfusion treatment. Then, transcriptome sequencing was used to analyse lung tissues. Autophagy inhibition (3-MA) and Rac1-overexpression transfection plasmids were used in BEAS-2B cells, and BEAS-2B cells were subjected to hypoxia reoxygenation (H/R) and sevoflurane treatment. In both animal tissue and cells, inflammatory cytokines and apoptotic and autophagy molecules were measured by quantitative real-time PCR, western blotting and immunostaining. As a result, decreased arterial partial oxygen and damage to the histological structure of lung tissues were observed in LIRI model rats, and these effects were reversed by sevoflurane treatment. Activation of inflammation (elevated IL-1ß, IL-6, and TNF-α) and apoptosis (elevated cleaved caspase3/caspase3 and Bax, degraded expression of Bcl2) and inhibition of autophagy (elevated P62, degraded expression of Beclin1 and LC3-II/LC3I) in the model group were ameliorated by sevoflurane. Transcriptome sequencing indicated that the PI3K/Akt pathway regulated by Rac1 plays an important role in LIRI. Furthermore, overexpression of Rac1 in a cell line inhibited the protective effect of sevoflurane in LIRI. Autophagy inhibition (3-MA) also prevented the protective effect of sevoflurane on inflammation and apoptosis. As shown in the present study, sevoflurane enhances autophagy via Rac1/PI3K/AKT signalling to attenuate lung ischaemia‒reperfusion injury.