Effect of long-term use of simvastatin on AQP5 expression in a rat model of ventilator-induced lung injury

Abstract

Objective To evaluate the effect of long-term use of simvastatin on aquaporin 5 (AQP5) expression in a rat model of ventilator-induced lung injury. Methods Thirty-two adult male Sprague-Dawley rats, weighing 250–280 g, were randomly divided into 4 groups (n= 8 each) using a random number table: control group (group C), simvastatin group (group Sim), mechanical ventilation group (group MV) and simvastatin + mechanical ventilation group (group SMV). In C and Sim groups, normal saline 1 ml/d and simvastatin 10 mg·kg–1·d–1 were injected, respectively, through a gastric tube into stomach for 4 weeks, and then the rats were tracheostomized, and mechanically ventilated, and the animals kept spontaneous breathing for 4 h. In MV and SMV groups, normal saline 1 ml/d and simvastatin 10 mg·kg–1·d–1were injected, respectively, through a gastric tube into stomach for 4 weeks, and then the rats were tracheostomized, and mechanically ventilated (tidal volume 50 ml/kg) for 4 h. The rats were then sacrificed, and lungs were removed for determination of wet to dry lung weight ratio (W/D ratio), activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), malondialdehyde (MDA) content, and expression of AQP5 protein and mRNA in lung tissues, and for microscopic examination of pathological changes. Results Compared with group C, the W/D ratio, MPO activity, and MDA content were significantly increased, the SOD activity was decreased, and the expression of AQP5 protein and mRNA was down-regulated in group MV (P<0.01). Compared with group MV, the W/D ratio, MPO activity, and MDA content were significantly decreased, the SOD activity was increased, and the expression of AQP5 protein and mRNA was up-regulated in group SMV (P<0.01). The pathological changes of lungs were significantly mitigated in group SMV as compared with group MV. Conclusion Long-term use of simvastatin alleviates ventilator-induced lung injury, and the mechanism is related to down-regulated expression of AQP5 in rats. Key words: Simvastatin; Respiration, artificial; Respiratory distress syndrome, adult; Aquaporin 5