Effect of dexmedetomidine pretreatment on JAK/STAT signaling pathway during myocardial injury induced by liver ischemia-reperfusion in rats

Abstract

Objective To investigate the effect of dexmedetomidine pretreatment on Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway during myocardial injury induced by liver ischemia-reperfusion(I/R)in rats. Methods Twenty-four healthy adult male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were divided into 3 groups(n=8 each)using a random number table method: sham operation group(group S), liver I/R group(group I/R), and dexmedetomidine pretreatment group(group D). The portal vein, superior and inferior vena cava, subhepatic inferior vena cava and hepatic artery were clamped, and the liver was perfused with 4 ℃ lactated Ringer′s solution for 60 min through the portal vein to establish the model of liver cold I/R in anesthetized rats.Dexmedetomidine 100 μg/kg was intraperitoneally injected at 30 min before ischemia in group D. Blood samples were collected at 8 h of reperfusion from the inferior vena cava for determination of serum cardiac troponin Ⅰ (cTnI) and heart-type fatty acid binding protein(H-FABP)concentrations(using the automatic biochemistry analyzer), tumor necrosis factor-alpha(TNF-α)and high-mobility group box 1 protein(HMGB1)concentrations(by enzyme-linked immunosorbent assay). The rats were then sacrificed, and hearts were harvested for examination of histopathological changes(with a light microscope)and for determination of the malondialdehyde(MDA)content(using thiobarbituric acid method)and superoxide dismutase(SOD)activity(by xanthine oxidase method), and expression of phosphorylated STAT1 and STAT3(p-STAT1, p-STAT3)and phosphorylated JAK2(p-JAK2)in myocardial tissues(by Western blot). Results Compared with group S, the serum concentrations of cTnI, H-FABP, TNF-α and HMGB1 were significantly increased, the MDA content was increased, the SOD activity was decreased, and the expression of p-JAK2, p-STAT1 and p-STAT3 was up-regulated in I/R and D groups(P<0.05). Compared with group I/R, the serum concentrations of cTnI, H-FABP, TNF-α and HMGB1 were significantly decreased, the MDA content was decreased, the SOD activity was increased, the expression of p-JAK2, p-STAT1 and p-STAT3 was down-regulated(P<0.05), and pathological changes of myocardium were significantly attenuated in group D. Conclusion The mechanism by which dexmedetomidine pretreatment mitigates myocardial injury induced by liver cold I/R may be related to inhibiting activation of JAK/STAT signaling pathway in rats. Key words: Dexmedetomidine; Reperfusion injury; Liver; Myocardium; Janus kinase; Activating transcription factor