Effect of dexmedetomidine on expression of aquaporin 5 in lung tissues in a rat model of ventilator-induced lung injury

Abstract

Objective To evaluate the effect of dexmedetomidine on the expression of aquaporin 5(AQP5)in lung tissues in a rat model of ventilator-induced lung injury. Methods One hundred pathogen-free male Sprague-Dawley rats, weighing 270-320 g, were divided into 5 groups(n=20 each)using a random number table: control group(group C), mechanical ventilation group(group V)and different doses of dexmedetomidine groups(DEX1-3 groups). The animals were mechanically ventilated, with tidal volume 40 ml/kg, respiratory rate 50 breaths/min, inspiratory/expiratory ratio 1∶1, and inspired oxygen fraction ratio 21%.In DEX1-3 groups, dexmedetomidine 0.5, 1.0 and 2.0 μg/kg were infused intravenously, respectively, over 20 min before ventilation, and then dexmedetomidine was infused intravenously for 4 h at a rate of 0.5, 1.0 and 2.0 μg·kg-1·h-1, respectively, during ventilation.Immediately before tracheal intubation and at 1, 2 and 4 h of ventilation, blood samples were collected from the femoral artery for blood gas analysis, and arterial oxygen partial pressure(PaO2)was recorded.At 4 h of ventilation, the animals were sacrificed, and the lungs were removed for examination of the pathological changes of lung tissues(with light microscope)and for determination of lung permeability index(LPI), wet/dry weight ratio(W/D ratio)and expression of p38 mitogen-activated protein kinase(p38MAPK), phosphorylated p38MAPK(p-p38MAPK)and AQP5 in lung tissues(by Western blot). The p-p38MAPK/p38MAPK ratio was calculated.The expression of AQP5 mRNA in lung tissues was detected by real-time polymerase chain reaction. Results Compared with group C, PaO2 was significantly decreased, W/D ratio and LPI were increased, the expression of p-p38MAPK was up-regulated, and p-p38MAPK/p38MAPK ratio was increased, and the expression of AQP5 protein and mRNA was down-regulated in V and DEX1 groups(P 0.05). Compared with group V, PaO2 was significantly increased, W/D ratio and LPI were decreased, the expression of p-p38MAPK was down-regulated, and p-p38MAPK/p38MAPK ratio was decreased, and the expression of AQP5 protein and mRNA was up-regulated in DEX2, 3 groups(P 0.05). The pathological changes of lung tissues were significantly attenuated in DEX2, 3 groups as compared with group V. Conclusion The mechanism by which dexmedetomidine mitigates ventilator-induced lung injury may be related to inhibition of p38MAPK phosphorylation and up-regulation of AQP5 expression in rats. Key words: Dexmedetomidine; Aquaporin 5; Respiration, artificial; Respiratory distress syndrome, adult