Protection Of Dexmedetomidine In Mice With Lipopolysaccharide Induced Acute Lung Injury

Background:Dexmedetomidine (Dex) is widely used for sedation in intensive care units and can be used as an adjunct to anesthetics. Moreover, previous studies have demonstrated that Dex has anti-inflammatory property. In this study, we aims to explore the potential therapeutic effects of Dex on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Mice were randomly divided into the control group, LPS group, Dex (25?g/kg)+LPS group, Dex (50?g/kg)+LPS group, and dexamethasone (1 mg/kg)+LPS group. To induce ALI, specific pathogen-free mice were intraperitoneally injected with LPS. Drugs were treated 1 h before LPS injection. The bronchoalveolar lavage fluid (BALF) samples were acquired to quantify protein concentrations. Lung tissues were harvested 6 h after lipopolysaccharide challenge, and the wet /dry lung ratio (W/D) was calculated. Lungs were used for histologic evaluation by hematoxylin and eosin staining and the lung injury was graded using a modified ALI score. The BCA method was employed to measure the protein concentration in the BALF, and the levels of mouse tumor necrosis factor-? (TNF-?), interleukin (IL)-1? and myeloperoxidase (MPO) were determined using Enzyme-linked immunosorbent assay kits. TNF-? and IL-6 mRNA expression were determined using quantitative real-time PCR. The activation of mitogen-activated protein kinase (MAPK) was explored by Western blot.Results:We found that pretreatment with Dex significantly reduced LPS-induced protein effusion in the BALF, as well as inhibited production of cytokines (TNF-?, IL-6 and MPO), and considerably reduced neutrophil infiltration, pulmonary haemorrhage and edema. In addition, we observed that the molecular mechanism of Dex-mediated anti-inflammation is probably associated with suppressing activation of MAPK signaling and p38 MAPK-HSP27 signaling.Conclusions:Dex significantly attenuated LPS-leaded into inflammatory factors production by inhibiting MAPK activation. Therefore, Dex may be developed as a preventive agent for lung inflammatory diseases, especially for ALI.