Dexmedetomidine Alleviates Pulmonary Edema by Modulating Na,K-ATPase in a Rat Model of Acute Lung Injury via the α2AR/PI3K/Akt Signaling Pathway

Background: Our previous studies have shown that Dexmedetomidine (Dex), an alpha 2adrenergic receptor (alpha 2AR) agonist, allevi-ates pulmonary edema in LPS-induced acute lung injury (ALI), but the mechanism is not clear. The aim of this study was to explore the underlying mechanisms by which Dex alleviates pulmonary edema.Methods: We established a rat model of acute lung injury (ALI) and alveolar epithelial cell injury induced by lipopolysaccharide (LPS) in A549 cells. Histology of the lungs was assayed with H&E staining, and the lung injury score was calculated. PaO2, PaO2/FiO2, the lung wet/dry (W/D) ratio and total protein in bronchoalveolar lavage fluid (BALF) and alveolar fluid clearance (AFC) were measured. The concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in serum and BALF and myeloperoxidase (MPO) activity in lung tissues and neutrophils in BALF were determined. The ex-pression of alpha 1Na,K-ATPase, beta 1Na,K-ATPase, phosphorylated phosphoinositide-3 kinase (p-PI3K) and phosphorylated protein kinase-B (p-Akt) in vivo and in vitro was analyzed.Results: Dex significantly alleviated the lung W/D ratio and total protein concentration in BALF and increased AFC, PaO2 and PaO2/FiO2. In addition, Dex reduced the concentrations of TNF-alpha, IL-beta and IL-6 and decreased the MPO activity in lung tissues and the number of neutrophils in BALF. Dex also increased the expression of alpha 1Na,K-ATPase, beta 1Na,K-ATPase, p-PI3K, and p-Akt in vivo and in vitro. However, these effects were partially reversed by the alpha 2AR inhibitor yohimbine or the PI3K inhibitor LY294042.Conclusions: These results demonstrated that Dex attenuated pulmonary edema by stimulating AFC and reduced alveolar ep-ithelial leakage by upregulating the expression of the Na,K-ATPase, and the mechanism is related to the alpha 2AR/PI3K/Akt signaling pathway in LPS-induced ALI.