Synthetic LXR agonist T0901317 attenuates lipopolysaccharide-induced acute lung injury in rats

摘要

Objective To investigate the potential role of synthetic liver X receptors (LXRs) agonists T0901317 in lung of rats with acute lung injury induced by lipopolysaccharide (LPS). Methods Rats infused with LPS served as acute lung injury (ALI) models. Specific mRNA was quantified by semi-quantitative reverse transcription polymerase (RT-PCR) and protein expression by western blotting. Inflammatory cytokine and MPO activity assays were studied by ELISA. Histopathology analysis was evaluated by hematoxylin and eosin. Results The expressions of LXRα and LXRβ were gradually decreased after LPS challenge. T0901317 pretreatment efficiently reduced the production of TNF-α, IL-1β, and IL-6, while elevated the level of IL-10 in BALF of rats with ALI. T0901317 also decreased the number of inflammatory cells and the concentration of total proteins in the BALF. Compared with the LPS group, rats with ALI which were pretreated with T0901317 had lower pulmonary tissue MPO activity and lightened histopathologic changes of lung. Furthermore, the expressions of NF-κB and ICAM-1 were markedly reduced after T0901317 administration. Conclusion The expressions of LXRs were significantly decreased and synthetic agonist T0901317 suppresses lung inflammatory responses and lightened histopathologic changes of lung in rats with ALI. The mechanisms of this action for T0901317 may associate with the inhibition of NF-κB activation and downregulation of adhesion molecules ICAM-1 gene.