雾化吸入布地奈德混合沙丁胺醇对单肺通气兔萎陷侧肺组织HIF-1α/VEGF信号通路的影响

Effect of inhaled aerosolized budesonide and salbutamol on HIF-1α/VEGF signaling pathway in collapsed lung tissues of rabbits undergoing one-lung ventilation

目的评价雾化吸入布地奈德混合沙丁胺醇对单肺通气兔萎陷侧肺组织缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路的影响。方法健康雄性新西兰大白兔24只,5~6月龄,体重2.5~3.0 kg。采用随机数字表法分为3组(n=8):双肺通气组(TLV组)、单肺通气组(OLV组)和布地奈德混合沙丁胺醇雾化吸入组(S+B组)。TLV组双肺通气3 h,余2组左侧单肺通气2 h,双肺通气1 h。S+B组于单肺通气前雾化吸入沙丁胺醇0.15 mg/kg+布地奈德1 mg+生理盐水共2 ml。TLV组与OLV组均吸入等量生理盐水。各组均采用容量控制通气模式,于雾化吸入前(T0)、雾化吸入结束即刻(T1)、通气1、2和3 h(T2-4)时采集动脉血样行血气分析,通气结束后处死动物,取萎陷侧肺下叶组织,光镜下观察肺组织病理学结果并行病理学损伤评分;采用Western blot法检测肺组织HIF-1α和VEGF的表达。结果与TLV组比较,OLV组和S+B组T2-4时氧合指数下降,乳酸浓度增高,肺组织病理学损伤评分升高,HIF-1α和VEGF表达上调(P<0.05);与OLV组比较,S+B组T2-4时氧合指数升高,乳酸浓度下降,肺组织病理学损伤评分降低,HIF-1α和VEGF表达下调(P<0.05)。结论雾化吸入布地奈德混合沙丁胺醇减轻单肺通气兔萎陷侧肺损伤的机制与阻断肺组织HIF-1α/VEGF信号通路有关。

Objective To evaluate the effect of inhaled aerosolized budesonide and salbutamol on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway in collapsed lung tissues of rabbits undergoing one-lung ventilation(OLV).Methods Twenty-four healthy male New Zealand white rabbits,aged 5-6 months,weighing 2.5-3.0 kg,were randomized into 3 groups(n=8 each)using a random number table method:two-lung ventilation(TLV)group,OLV group,and budesonide and salbutamol aerosol inhalation group(group B+S).Bilateral lungs were ventilated for 3 h in group TLV,and the left lung was ventilated for 2 h followed by 1-h TLV in group OLV and B+S group.In group B+S,aerosolized salbutamol 0.15 mg/kg and budesonide 1 mg in normal saline(2 ml in total)was inhaled before OLV.The equal volume of normal saline was given instead in TLV and OLV groups.Volume-controlled ventilation was used in each group.Before beginning of aerosol inhalation(T0),immediately after the end of aerosol inhalation(T1),and at 1,2 and 3 h of ventilation(T2-4),arterial blood samples were obtained for blood gas analysis.Oxygenation index was calculated.The rabbits were sacrificed at the end of ventilation,and lower lobe tissues were obtained from the collapsed lung for examination of the pathological changes(with a light microscope)which were scored and for determination of HIF-1αand VEGF expression in lung tissues(by Western blot).Results Compared with group TLV,oxygenation index was significantly decreased at T2-4,the concentration of lactic acid and lung injury score were increased,and the expression of HIF-1αand VEGF was up-regulated in group OLV and group B+S(P<0.05).Compared with group OLV,oxygenation index was significantly increased at T2-4,the concentration of lactic acid and lung injury score were decreased,and the expression of HIF-1αand VEGF was down-regulated in group S+B(P<0.05).Conclusion The mechanism by which inhaled aerosolized budesonide and salbutamol reduces OLV-induced injury to the collapsed lung is related to blocking HIF-1α/VEGF signaling pathway in lung tissues of rabbits.