Effect of ulinastatin pretreatment on expression of aquaporin 1 and 5 in rats with acute lung injury induced by cardiopulmonary bypass

Objective To evaluate the effect of ulinastatin(UTI)on the expression of aquaporin 1(AQP1)and AQP5 in rats with acute lung injury induced by cardiopulmonary bypass(CPB). Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 3 groups(n=16 each)using a random number table method: sham operation group(Sham group), CPB group and UTI group.UTI 200 000 U/kg was injected intravenously at 10 min prior to CPB in UTI group.The model of CPB was established in CPB and UTI groups.The equal volume of normal saline was intravenously injected at 10 min prior to puncture or at 10 min prior to CPB in Sham and CPB groups.Rats were sacrificed, and lung tissues were excised for determination of weight to dry weight ratio(W/D ratio), expression of AQP1 and AQP5(by immunohistochemistry), expression of AQP1 and AQP5 protein and mRNA(by real-time polymerase chain reaction or Western blot)and for examination of morphological structure(with a light microscope)and ultrastructure of lung tissues(with an electron microscope). Injured alveolar rate(IAR)and rates of AQP1 and AQP5 positive cells were calculated. Results Compared with Sham group, W/D ratio and IAR were significantly increased, rates of AQP1 and AQP5 positive cells were decreased, and the expression of AQP1 and AQP5 protein and mRNA was down-regulated in CPB and UTI groups (P<0.05). Compared with CPB group, W/D ratio and IAR were significantly decreased, rates of AQP1 and AQP5 positive cells were increased, and the expression of AQP1 and AQP5 protein and mRNA was up-regulated in UTI group(P<0.05). The injury to morphological structure and ultrastructure was significantly attenuated in UTI group when compared with CPB group. Conclusion The mechanism by which UTI pretreatment reduces CPB-induced acute lung injury is related to up-regulating the expression of AQP1 and AQP5 in rats. Key words: Trypsin inhibitors; Cardiopulmonary bypass; Respiratory distress syndrome, adult; Aquaporin 1; Aquaporin 5