Dexmedetomidine reduces ventilator-induced lung injury via ERK1/2 pathway activation.

Abstract

Mechanical ventilation (MV) can contribute to ventilator-induced lung injury (VILI); dexmedetomidine (Dex) treatment attenuates MV-related pulmonary inflammation, but the mechanisms remain unclear. Therefore, the present study aimed to explore the protective effect and the possible molecular mechanisms of Dex in a VILI rodent model. Adult male Sprague-Dawley rats were randomly assigned to one of seven groups (n=24 rats/group). Rats were euthanized after 4 h of continuous MV, and pathological changes, lung wet/dry (W/D) weight ratio, the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6) in the bronchoalveolar lavage fluid (BALF), and the expression levels of Bcl-2 homologous antagonist/killer (Bak), Bcl-2, pro-caspase-3, cleaved caspase-3 and the phosphorylation of ERK1/2 in the lung tissues were measured. Propidium iodide uptake and TUNEL staining were used to detect epithelial cell death. The Dex pretreatment group exhibited fewer pathological changes, lower W/D ratios and lower expression levels of inflammatory cytokines in BALF compared with the VILI group. Dex significantly attenuated the ratio of Bak/Bcl-2, cleaved caspase-3 expression levels and epithelial cell death, and increased the expression of phosphorylated ERK1/2. The protective effects of Dex could be partially reversed by PD98059, which is a mitogen-activated protein kinase (upstream of ERK1/2) inhibitor. Overall, dexmedetomidine was found to reduce the inflammatory response and epithelial cell death caused by VILI, via the activation of the ERK1/2 signaling pathway.