Endothelin-1 Recepter Antagonist BQ-123 Reduces Lung Injury During One-lung Ventilation via Regulating PI3K-Akt-HIF-1α Signaling Pathway in Rabbits
Objective To investigate the effect of regulation of PIK3-Akt-HIF-1 signaling pathway on alleviating lung injury in rabbits pretreated with the endothelin-1 receptor antagonist BQ-123 during one-lung ventilation.Methods 20 Japanese big-ear rabbits(no limit of male or female)were randomly divided into the control group,OLV group,OLV+BQ-123 group,OLV+BQ-123+LY249002 group,with 5 rabbits in each.Rabbits in the control group were continuously ventilated with both lungs for 2.5 h,and OLV group,OLV+BQ-123 group,OLV+BQ-123+LY249002 group were taken OLA on the right side for 2 hours,and then resumed with two lungs for 2.5 hours.Rabbits in OLA+BQ-123 group and OLA+BQ-123+LY294002 group were injected with BQ-123 50 μg/kg through femoral vein about 10 minute before OLA,and OLV+BQ-123+LY294002 group was given intravenous infusion of phosphatidylinositol 3-kinase(PI3K)specific inhibitor(LY294002)0.3 mg/kg before BQ-123 administration,the infusion time was 5 min.The left lung tissue was retained and weighed to calculate the wet-to-dry ratio(W/D),and pathological sections were performed to evaluate the degree of lung injury after the experiment;the protein expression of phosphorylated serine-threonine protein kinase(p-Akt)and hypoxia-inducible factor-1 alpha(HIF-1α)were detected by Western blot.Results Compared with the control group,the pulmonary edema status,W/D and lung injury pathological score were increased,and the relative protein expression of p-Akt and HIF-1α were down-regulated in OLA group(all P＜0.05);after pretreatment intervention with BQ-123,the lung injury degree and W/D decreased and the relative protein expres-sion of p-Akt and HIF-1α were upregulated(all P＜0.05)in OLV+BQ-123 group,the lung injury degree and W/D decreased and the relative protein expression of p-Akt and HIF-1α were upregulated(all P＜0.05)in OLA+BQ group compared with OLA+BQ-123+LY294002 group.Conclusion Endothelin-1 recepter antagonist BQ-123 can reduces the damage to unventilated lung during one-lung ventilation through activiating PI3K-Akt-HIF-1α signaling pathway in rabbits.
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