韩霜; 何锟; 蔚冬冬; 胡玉敬; 吴亚敬; 容俊芳

doi:10.3760/cma.j.issn.0254-1416.2019.11.010

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• 麻醉并发症 •

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

中华麻醉学杂志, 2019,39(11) : 1315-1318. DOI: 10.3760/cma.j.issn.0254-1416.2019.11.010

摘要

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(T_2-4)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T_2-4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T_2-4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。

引用本文: 韩霜, 何锟, 蔚冬冬, 等. 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 [J] . 中华麻醉学杂志, 2019, 39(11) : 1315-1318. DOI: 10.3760/cma.j.issn.0254-1416.2019.11.010.

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长时间单肺通气、萎陷侧肺复张均可造成急性肺损伤^[1]。单肺通气时萎陷侧肺血流未得到充分氧合，通气/血流比例降低，而导致低氧血症，且萎陷侧肺复张缺氧后复氧可发生肺组织炎症反应^[2,3]。缺氧诱导因子-1α(HIF-1α)是介导缺氧反应中的主要调控因子^[4]。HIF-1α作为血管内皮生长因子(VEGF)的上游调节因子，在缺氧诱导VEGF表达过程中发挥重要作用^[5]。研究表明，HIF-1α、VEGF和AQP-1参与了缺氧引起肺损伤的病理过程^[6]。术前单纯雾化吸入布地奈德可减少单肺通气时肺炎症反应^[7]。而沙丁胺醇可激动支气管平滑肌细胞的β₂受体，扩张支气管；降低肺泡毛细血管通透性，抑制炎症渗出水肿，改善肺功能^[8]。单肺通气前雾化吸入布地奈德混合沙丁胺醇是否通过阻断肺组织HIF-1α/VEGF信号通路减轻肺损伤尚不清楚。本研究拟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HIF-1α/VEGF信号通路的影响。

贡献者信息

韩霜

河北省人民医院麻醉科，石家庄　050051

何锟

石家庄市第四医院麻醉科　050000

蔚冬冬

河北省人民医院麻醉科，石家庄　050051

胡玉敬

河北省人民医院麻醉科，石家庄　050051

吴亚敬

河北省人民医院麻醉科，石家庄　050051

容俊芳

河北省人民医院麻醉科，石家庄　050051

通信作者

容俊芳

河北省人民医院麻醉科，石家庄　050051

Email：rffl3291@163.com

关键词

单肺通气; 急性肺损伤; 布地奈德; 沙丁胺醇; 支气管扩张药; 投药，吸入;

作者声明

韩霜和何锟对本文有同等贡献

利益冲突

利益冲突　所有作者均声明不存在利益冲突

历史

出版日期：2019-11-20

收稿日期：2019-04-23

本文编辑

葛胜辉

Complication of Anesthesia

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

Shuang Han, Kun He, Dongdong Yu, Yujing Hu, Yajing Wu, Junfang Rong

Published 2019-11-20

Cite as Chin J Anesthesiol, 2019, 39(11): 1315-1318. DOI: 10.3760/cma.j.issn.0254-1416.2019.11.010

Abstract

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 (T_2-4), 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-1α and VEGF expression in lung tissues (by Western blot).

Results

Compared with group TLV, oxygenation index was significantly decreased at T_2-4, the concentration of lactic acid and lung injury score were increased, and the expression of HIF-1α and VEGF was up-regulated in group OLV and group B+ S (P<0.05). Compared with group OLV, oxygenation index was significantly increased at T_2-4, the concentration of lactic acid and lung injury score were decreased, and the expression of HIF-1α and 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.

Key words:

One-lung ventilation; Acute lung injury; Budesonide; Albuterol; Bronchodilator agents; Administration, inhalation

Contributor Information

Shuang Han