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

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.

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Cat.No. Product Name Information Publications Customer Product Validation
S1177 PD98059 PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist. (404) (10)

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