Dexmedetomidine attenuates acute lung injury induced by lipopolysaccharide in mouse through inhibition of MAPK pathway

Dexmedetomidine (Dex) is widely used for sedation in intensive care units and can be used as an adjunct to anesthetics. Previous studies have demonstrated that Dex has anti-inflammatory property. In this study, we aim to explore the potential therapeutic effects and mechanisms of Dex on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To induce ALI, mice were intraperitoneally injected with LPS, while Dex was treated 1 h before LPS injection. The inflammation of lung tissues was evaluated by HE stain, and bronchoalveolar lavage fluid (BALF) was obtained after 6 h to measure protein concentrations. We also used an enzyme-linked immunosorbent assay to detect the secretion levels of proinflammatory cytokines in the serum. Western blotting method was adopted to observe changes in mitogen-activated protein kinases and downstream nuclear transcription factors. The results showed that pretreatment with Dex considerably reduced neutrophil infiltration and pulmonary edema, and significantly reduced protein concentrations in the BALF, as well as suppressed LPS-induced elevation of proinflammatory cytokines (TNF-alpha and IL-1 beta) in the serum. In addition, we observed that the molecular mechanism of Dex-mediated anti-inflammation is associated with decreasing phosphorylation of MKK4, MMK3/6, ERK1/2, p38MAPK, and JNK, and diminishing activation of Elk-1, c-Jun, and ATF-2. Dex could attenuate ALI induced by LPS in mice, and this effect may be mediated through the inhibition of MAPK pathway.