Dexmedetomidine Protects Against Lps-Induced Lung Injuries In Mice Through Alleviation Of Inflammation And Oxidative Stress

Objective: The aim of this study was to assess the protective effects of dexmedetomidine on acute lung injuries (ALI), examining its underlying mechanisms. Methods: A mouse ALI model was reproduced by intra-tracheal administration of lipopolysaccharide (LPS 2 mg/kg). Mice were randomly divided into four groups: control group; LPS group, LPS+dex 20 mu g/kg group, and LPS+dex 40 mu g/kg group. Lung wet/dry weight ratios were examined, as well as myeloperoxidase (MPO) activity. The content of malondialdehyde (MDA) and levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissues were also determined. In addition, levels of tumor necrosis factoralpha (TNF-alpha) and IL-6, as well as total protein concentrations in bronchoalveolar lavage fluid (BALF), were assayed. Results: The present study found that lung tissues from the LPS group were significantly damaged, while single-dose dexmedetomidine treatment significantly and dose-dependently attenuated LPS-induced ALI with decreased histopathological damage, lung wet/dry weight ratios, and MPO activity. Levels of IL-6 and TNF-alpha, as well as total protein concentrations in BALF, were elevated by LPS challenge and dose-dependently alleviated by dexmedetomidine treatment. The content of MDA was increased, while levels of SOD and GSH were decreased in LPS challenged lung tissues. These effects were partially reversed by dexmedetomidine treatment. Furthermore, dexmedetomidine inhibited TLR4 expression and activation of NF-kappa B in lung tissues. Conclusion: Present findings suggest that dexmedetomidine may exert protective effects against LPS-induced ALI in mice by reducing inflammatory response and oxidative stress. TLR4/NF-kappa B pathway suppression may play a role in the underlying mechanisms.