Effect of dexmedetomidine pretreatment on activation of JAK/STAT signaling pathway during intestinal injury in rats undergoing liver transplantation

Abstract

Objective To evaluate the effect of dexmedetomidine pretreatment on activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway during intestinal injury in rats undergoing liver transplantation. Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats, weighing 220-250 g, aged 8-10 weeks, were divided into 4 groups (n=8 each) using a random number table: sham operation group (S group), liver transplantation group (LT group), dexmedetomidine pretreatment group (D group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (D+ A group). The model of liver transplantation was established in LT, D and D+ A groups except group S. In group D, dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min before skin incision.In group D+ A, atipamzole 250 μg/kg was injected intraperitoneally at 5 min before administration of dexmedetomidine.At 6 h of reperfusion, blood samples were collected from the inferior vena cava for determination of serum concentrations of intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 protein (HMGB1). Intestinal specimens were then obtained for examination of the pathological changes of intestinal tissues (under light microscope) and for determination of the expression of activated caspase-3, phosphorylated JAK2 (p-JAK2), phosphorylated STAT1 (p-STAT1) and phosphorylated STAT3 (p-STAT3). Intestinal damage was assessed and scored.Wet/dry weight ratio (W/D ratio) was calculated. Results Compared with group S, the concentrations of iFABP, LPS, TNF-α and HMGB1 in serum, intestinal damage scores and W/D ratio were significantly increased, and the expression of activated caspase-3, p-JAK2, p-STAT1 and p-STAT3 in intestinal tissues was up-regulated in LT and D groups (P<0.05). Compared with group LT, the concentrations of iFABP, LPS, TNF-α and HMGB1 in serum, intestinal damage scores and W/D ratio were significantly decreased, and the expression of activated caspase-3, p-JAK2, p-STAT1 and p-STAT3 in intestinal tissues was down-regulated in group D (P<0.05). Compared with group D, the concentrations of iFABP, LPS, TNF-α and HMGB1 in serum, intestinal damage scores and W/D ratio were significantly increased, and the expression of activated caspase-3, p-JAK2, p-STAT1 and p-STAT3 in intestinal tissues was up-regulated in group D+ A (P<0.05). The pathological changes of intestinal tissues were significantly attenuated in group D as compared with group LT. Conclusion The mechanism by which dexmedetomidine pretreatment reduces intestinal injury may be related to inhibition of JAK/STAT signaling pathway activation in rats undergoing liver transplantation. Key words: Janus kinases; STAT transcription factors; Dexmedetomidine; Reperfusion injury; Liver transplantation; Intestines