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 / 中华麻醉学杂志

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 tablecontrol 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.