Effect of dexmedetomidine on JAK2/STAT3 signaling pathway in mice with endotoxin-induced acute lung injury

Abstract

Objective To evaluate the effect of dexmedetomidine on janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in mice with endotoxin-induced acute lung injury (ALI). Methods Twenty-four male C57BL/6 mice, weighing 20-25 g, were randomly divided into 3 groups (n=8 each) using a random number table: control group (group C), endotoxin-induced ALI group (group ALI), and dexmedetomidine group (group Dex). ALI was induced with lipopolysaccharide (LPS) 5 mg/kg injected intraperitoneally.Dexmedetomidine 40 μg/kg was injected intraperitoneally at 1 h after LPS injection in group Dex, while the equal volume of normal saline was given in C and ALI groups.At 6 h after LPS injection, blood samples were collected from the carotid artery to detect arterial oxygen partial pressure (PaO2). The mice were then sacrificed, and broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of total protein, interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). The lung tissues were removed for determination of wet to dry lung weight ratio (W/D ratio), and expression of phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), IL-1β mRNA, IL-6 mRNA and TNF-α mRNA, and for examination of the pathological changes which were scored. Results Compared with group C, the PaO2 was significantly decreased, and W/D ratio, lung injury score, concentrations of total protein, IL-1β, IL-6 and TNF-α in BALF, and expression of IL-1β, IL-6 and TNF-α mRNA, p-JAK2 and p-STAT3 were increased in ALI and Dex groups (P<0.05). Compared with group ALI, the PaO2 was significantly increased, and W/D ratio, lung injury score, concentrations of total protein, IL-1β, IL-6 and TNF-α in BALF, and expression of IL-1β, IL-6 and TNF-α mRNA, p-JAK2 and p-STAT3 were decreased in group Dex (P<0.05). Conclusion The mechanism by which dexmedetomidine attenuates LPS-induced ALI is probably related to inhibition of activation of JAK2/STAT3 signaling pathway in mice. Key words: Dexmedetomidine; Endotoxemia; Respiratory distress syndrome, adult; Protein-tyrosine kinases; Activating transcription factor 3