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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2022年03期

页码:

316-322

栏目:

论著

出版日期:

2022-06-20

文章信息/Info

Title:

PM_2.5 aggravates lung injury by activating HIF-1α-NF-κB/VEGF pathway

作者:

林红卫; 李王平; 金发光

710038 西安,中国人民解放军空军军医大学第二附属医院呼吸与危重症医学科

Author(s):

Lin Hongwei;  Li Wangping;  Jin Faguang.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China

关键词:

肺损伤;  细颗粒物;  缺氧诱导因子-1;  核因子-κB;  血管内皮生长因子

Keywords:

Lung injury;  Particulate matter;  Hypoxia-inducible factors-1α;  Nuclear factor-κB;  Vascular enclothelial growth factor

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2022.03.006

摘要:

目的 分析HIF-1α在PM_2.5暴露致肺损伤中的影响。方法 构建经气管滴注PM_2.5悬液诱导大鼠肺损伤的动物模型,通过蛋白质免疫印迹、病理切片、ROS与TUNEL染色和ELISA等方法,分析不同PM_2.5暴露剂量下HIF-1α表达和肺损伤情况; 构建抑制HIF-1α表达的动物模型,通过蛋白质免疫印迹、免疫荧光和ELISA等方法探讨HIF-1α在PM_2.5暴露致肺损伤中的作用机制。结果 PM_2.5暴露造成肺组织病理性损伤,提高肺组织ROS水平、细胞凋亡率和湿干比,促进支气管肺泡灌洗液中各类炎症细胞计数和炎症因子IL-6、TNF-α水平增高,激活肺组织HIF-1α的蛋白表达,且以上效应与PM_2.5暴露浓度相关; 抑制HIF-1α可降低NF-κB表达,降低支气管肺泡灌洗液中炎症因子水平,改善肺组织炎症; 抑制HIF-1α可降低VEGF表达,降低支气管肺泡灌洗液中白蛋白水平和肺组织湿干比,改善肺组织水肿。结论 PM_2.5通过激活“HIF-1α-NF-κB-炎症细胞(AMs、NEUs)/炎症因子(IL-6、TNF-α)-肺组织炎症反应”和“HIF-1α-VEGF-肺血管通透性-肺水肿”两条路径加重肺组织炎症反应、肺血管通透性和肺水肿,导致肺损伤。

Abstract:

Objective To explore the role of HIF-1α in PM_2.5-induced lung injury. Methods The rat model of lung injury induced by tracheal aerosol PM_2.5 suspension was established, HIF-1α expression and lung injury under different PM_2.5 exposure doses were investigated by western blot, pathological section, ROS staining, TUNEL staining and ELISA. An animal model was constructed to inhibit HIF-1α expression, and the mechanism of HIF-1α in lung injury induced by PM_2.5 exposure was investigated by western blot, immunofluorescence and ELISA. Results PM_2.5 exposure causes pathological damage, increases ROS level, apoptosis rate and wet-dry ratio of lung tissue, promotes the count of various inflammatory cells and the levels of inflammatory factors IL-6 and TNF-α in BALF, and activates the protein expression of HIF-1α in lung tissue, the above effects are related to PM_2.5 exposure concentration. Inhibition of HIF-1α can reduce lung inflammation by decreasing NF-κB expression in lung tissue and the level of inflammatory factors in BALF. Inhibition of HIF-1α can reduce lung tissue edema by decreasing VEGF expression in lung tissue, albumin level in BALF and lung tissue wet-dry ratio. Conclusion PM_2.5 aggravates lung tissue inflammation, pulmonary vascular permeability and pulmonary edema by activating two pathways: HIF-1α-NF-κB-inflammatory cells(AMs, NEUs)/inflammatory factors(IL-6, TNF-α)-lung tissue inflammation and HIF-1α-VEGF-pulmonary vascular permeability-pulmonary edema.

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备注/Memo

备注/Memo:

基金项目: 陕西省重点研发计划(2018ZDCXL-SF-02-03-02)
通信作者: 金发光, Email: jinfag@fmmu.edu.cn

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更新日期/Last Update: 2022-06-20