Effects of dexmedetomidine on expression of aquaporins 1 and 5 during lung ischemia/reperfusion in rats: an in vitro experiment

Abstract

Objective To evaluate the effects of dexmedetomidine on the expression of aquaporins 1 (AQP1) and AQP5 during lung ischemia/reperfusion (I/R) in rats in an in vitro experiment. Methods SPF healthy male Sprague-Dawley rats, aged 3-4 months, weighing 250-320 g, were used in this study.Forty-five isolated rat lungs in which the model of isolated lung perfusion was successfully established were divided into 3 groups (n= 15 each) using a random number table: sham operation group (S group), I/R group and dexmedetomidine group (D group). The isolated rat lungs were continuously perfused for 150 min in group S. After 15 min of perfusion, the isolated rat lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in group I/R. In group D, the isolated rat lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine, and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetomidine.The lung compliance, airway resistance, perfusion flow and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15, 45 and 75 min after restoration of perfusion.Lung tissues were obtained at 75 min after restoration of perfusion for determination of wet/dry weight ratio (W/D ratio) and for examination of the pathological changes and changes in the ultrastructure.The expression of AQP1 and AQP5 protein and mRNA in lung tissues was detected by Western blot and real-time polymerase chain reaction, respectively. Results Compared with S group, the airway resistance was significantly increased and lung compliance, perfusion flow and PaO2 were decreased during reperfusion, and W/D ratio was increased in I/R and D groups (P<0.05), the expression of AQP1 and AQP5 protein and mRNA in lung tissues was significantly down-regulated in group I/R, and the expression of AQP1 and AQP5 protein and mRNA in lung tissues was significantly up-regulated in group D (P<0.05). Compared with I/R group, the airway resistance was significantly decreased and lung compliance, perfusion flow and PaO2 were increased during reperfusion, W/D ratio was decreased, the expression of AQP1 and AQP5 protein and mRNA in lung tissues was up-regulated (P<0.05), and the pathological changes of lung tissues was significantly attenuated in group D. Conclusion The mechanism by which dexmedetomidine reduces I/R injury may be related to up-regulation of the expression of AQP1 and AQP5 in rats in an in vitro experiment. Key words: Dexmedetomidine; Aquaporin 1; Aquaporin 5; Reperfusion injury; Lung