Department of Eastern Respiratory Medicine, Linyi People's Hospital, Linyi, China.
Linyi People's Hospital Office, Linyi People's Hospital, Linyi, China.
J Surg Res. 2019 Dec;244:358-367. doi: 10.1016/j.jss.2019.06.060. Epub 2019 Jul 16.
Ventilator-induced lung injury (VILI) in chronic obstructive pulmonary disease (COPD) is still a problem. We intended to explore the role of macrophage polarity in VILI and the underlying mechanism.
COPD model was created by cigarette smoke and ventilated. Macrophages were isolated, and the wet/dry (W/D) ratio was determined after modeling, and proteins in bronchoalveolar lavage fluid (BALF) were assessed by bicinchoninic acid assay. Histopathology was observed by Hematoxylin-Eosin staining. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured by enzyme-linked immunosorbent assay. Macrophage polarity was assessed by flow cytometry. Protein levels were measured by Western blot and mRNA by quantitative real-time polymerase chain reaction.
Pathology statement was worsened, and the W/D ratio, protein level in BALF, TNF-α level, and IL-6 levels were elevated in cigarette smoke-induced COPD model. Notch-1 intracellular domain, hairy and enhancer of split (Hes) 1, Hes5, hairy/enhancer-of-split related with YRPW motif protein 1, CD86, TNF-α, and inducible nitric oxide synthases expressions were raised, whereas CD206, IL-4, and IL-10 expressions were decreased in macrophages after ventilation, shifting macrophage polarity to M1 phenotype. After the inhibition of Notch signaling, pathology statement was improved, and the W/D ratio, protein level in BALF, TNF-α, IL-6, Notch-1 intracellular domain, Hes1, Hes5, hairy/enhancer-of-split related with YRPW motif protein 1, CD86, TNF-α, and inducible nitric oxide synthases expressions were decreased while CD206, IL-4, and IL-10 expressions were elevated after ventilation, shifting macrophage polarity to M2 phenotype partially.
Mechanical ventilation in cigarette-induced COPD could activate the Notch signal pathway and further shift the polarity of macrophage toward M1 phenotype, leading to VILI in cigarette-induced COPD.
慢性阻塞性肺疾病（COPD）患者的呼吸机相关性肺损伤（VILI）仍然是一个问题。本研究旨在探讨巨噬细胞极性在 VILI 中的作用及其潜在机制。
通过香烟烟雾和通气来建立 COPD 模型。建模后测定湿/干（W/D）比值，并通过双缩脲法测定支气管肺泡灌洗液（BALF）中的蛋白质。苏木精-伊红染色观察组织病理学变化。酶联免疫吸附试验测定肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6水平。通过流式细胞术评估巨噬细胞极性。通过 Western blot 测定蛋白水平，通过实时定量聚合酶链反应测定 mRNA 水平。
香烟烟雾诱导的 COPD 模型中，病理表现恶化，W/D 比值、BALF 蛋白水平、TNF-α水平和 IL-6 水平升高。Notch-1 胞内结构域、 hairy 和 enhancer of split（Hes）1、Hes5、 hairy/enhancer-of-split related with YRPW motif protein 1、CD86、TNF-α和诱导型一氧化氮合酶表达增加，而巨噬细胞通气后 CD206、IL-4 和 IL-10 表达减少，巨噬细胞极性向 M1 表型转变。Notch 信号通路被抑制后，病理表现改善，W/D 比值、BALF 蛋白水平、TNF-α、IL-6、Notch-1 胞内结构域、Hes1、Hes5、 hairy/enhancer-of-split related with YRPW motif protein 1、CD86、TNF-α和诱导型一氧化氮合酶表达降低，而巨噬细胞通气后 CD206、IL-4 和 IL-10 表达增加，巨噬细胞极性向 M2 表型部分转变。
香烟诱导的 COPD 患者机械通气可激活 Notch 信号通路，进一步使巨噬细胞极性向 M1 表型转变，导致香烟诱导的 COPD 中的 VILI。
