Effect of dexmedetomidine on JAK2/STAT3 signaling pathway in lung tissues in a rat model of cardiopulmonary bypass / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of dexmedetomidine on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in lung tissues in a rat model of cardiopulmonary bypass (CPB).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, weighing 320-350 g, aged 12-16 weeks, were randomly divided into sham operation group (group S), CBP group, and dexmedetomidine group (group Dex), with 8 rats in each group.In group Dex, dexmedetomidine was intravenously infused in a dose of 5 μg/kg starting from 15 min before CPB followed by infusion of 5 μg·kg -1·h -1 during CPB.Blood samples were collected at 2 h after the end of CPB for blood gas analysis, and oxygenation index (OI) and respiratory index (RI) were calculated.Then the rats were sacrificed by bloodletting.The lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)(by enzyme-linked immunosorbent assay), and expression of JAK2, STAT3, phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) (by Western blot). The p-JAK2/JAK2 and p-STAT3/STAT3 ratios were calculated. Results:Compared with group S, the lung injury score, W/D ratio and RI were significantly increased, OI was decreased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were increased in the other two groups ( P<0.05). Compared with group CPB, the lung injury score, W/D ratio and RI were significantly decreased, OI was increased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were decreased in group Dex ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates CPB-induced lung injury may be related to inhibiting JAK2/STAT3 signaling pathway and reducing inflammatory responses in lung tissues of rats.