Effect of dexmedetomidine on microRNA-155-hypoxia-inducible factor-1α-heme oxygenase-1 signaling pathway in a rat model of endotoxin-induced acute lung injury

Abstract

Objective To evaluate the effect of dexmedetomidine on microRNA(miRNA)-155-hypoxia-inducible factor-1α(HIF-1α)-heme oxygenase-1(HO-1)signaling pathway in a rat model of endotoxin-induced acute lung injury. Methods Forty adult male Wistar rats, weighing 220-250 g, were equally and randomly divided into 4 groups using a random number table: control group(group C), dexmedetomidine group(group D), endotoxin-induced acute lung injury group(group L), and endotoxin-induced acute lung injury+ dexmedetomidine group(group LD). Acute lung injury was induced by intraperitoneal lipopolysaccharide(LPS)5 mg/kg in L and LD groups.In D and LD groups, dexmedetomidine was infused in a loading dose of 1 μg·kg-1·h-1 for 10 min starting before intraperitoneal injection of normal saline or LPS followed by an infusion of 5 μg·kg-1·h-1 throughout the operation.At 6 h after normal saline or LPS injection, blood samples were taken from the carotid artery for detection of arterial oxygen partial pressure(PaO2). The left lung was lavaged, and broncho-alveolar lavage fluid(BALF)was collected for determination of concentrations of total protein, interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and intercellular adhesion molecule-1(ICAM-1). The rats were then sacrificed, and lungs were removed for determination of the wet to dry lung weight ratio(W/D ratio), mRNA expression of miR-155, IL-1β, TNF-α and ICAM-1, and protein expression of HIF-1α and HO-1, and for examination of the pathological changes which were scored. Results Compared with group C, the PaO2 was significantly decreased, and the W/D ratio, lung injury score, concentrations of total protein, IL-1β, TNF-α and ICAM-1 in BALF, mRNA expression of miR-155, IL-1β, TNF-α and ICAM-1, and protein expression of HIF-1α and HO-1 were significantly increased in L and LD groups(P<0.05). Compared with group L, the PaO2 and protein expression of HIF-1α and HO-1 were significantly increased, and the W/D ratio, lung injury score, concentrations of total protein, IL-1β, TNF-α and ICAM-1 in BALF, and mRNA expression of miR-155, IL-1β, TNF-α and ICAM-1 were significantly decreased in group LD(P<0.05). Conclusion Dexmedetomidine reduces endotoxin-induced acute lung injury through activating miR-155-HIF-1α-HO-1 signaling pathway in rats. Key words: Dexmedetomidine; Respiratory distress syndrome, adult; Endotoxemia; MicroRNAs; Hypoxia-inducible factor 1, alpha subunit; Heme oxygenase-1