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

Abstract

Background: Our previous studies have shown that Dexmedetomidine (Dex), an α₂adrenergic receptor (α₂AR) agonist, alleviates 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 α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum and BALF and myeloperoxidase (MPO) activity in lung tissues and neutrophils in BALF were determined. The expression of α₁Na,K-ATPase, β₁Na,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-α, IL-β and IL-6 and decreased the MPO activity in lung tissues and the number of neutrophils in BALF. Dex also increased the expression of α₁Na,K-ATPase, β₁Na,K-ATPase, p-PI3K, and p-Akt in vivo and in vitro. However, these effects were partially reversed by the α₂AR inhibitor yohimbine or the PI3K inhibitor LY294042. Conclusions: These results demonstrated that Dex attenuated pulmonary edema by stimulating AFC and reduced alveolar epithelial leakage by upregulating the expression of the Na,K-ATPase, and the mechanism is related to the α₂AR/PI3K/Akt signaling pathway in LPS-induced ALI.