INSERM, Unité U955 (Institut Mondor de Recherche Biomédicale), Créteil, 94010, France.
CHU Lille, Centre de Réanimation, F-59000 Lille, France.
Biomed Res Int. 2018 Dec 19;2018:5721293. doi: 10.1155/2018/5721293. eCollection 2018.
An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed. C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) or maintained on spontaneous ventilation (SV) during two hours. As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while bronchoalveolar lavage cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11b were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice. In an elastase-induced model of pulmonary emphysema, normal tidal volume mechanical ventilation may produce an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response seems to be observed only when the emphysema model shows an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11b
过度的肺部炎症反应可能解释了接受有创机械通气的慢性阻塞性肺疾病 (COPD) 患者预后不良的原因。本研究旨在评估弹性蛋白酶诱导的肺气肿小鼠模型中常规潮气量机械通气的反应。在该模型中，分析了两个时间点，这两个时间点与不同程度的肺部炎症相关，但肺破坏程度相似。C57BL/6 小鼠接受 5IU 猪胰弹性蛋白酶（弹性酶组）或相同体积的生理盐水（盐水组）气管内滴注。滴注后 14 天（D14）和 21 天（D21），小鼠麻醉后插管，接受机械通气（MV）或自主通气（SV）2 小时。与盐水组相比，弹性酶组在 D14 和 D21 时平均弦长和肺顺应性均增加，而支气管肺泡灌洗液细胞计数在两组之间无差异。在弹性酶和盐水组的机械通气期间，肺力学也发生了类似的改变。在 D14 时，弹性酶 SV 小鼠和弹性酶 MV 小鼠的肺实质中均存在激活的肺泡巨噬细胞 CD11b，但在 D21 时和盐水组中不存在，表明仅在 D14 时存在弹性酶的炎症状态。在 D14 时，与弹性酶 SV 小鼠相比，弹性酶 MV 小鼠的总肺中性粒细胞百分比显著增加。此外，与弹性酶 SV 小鼠相比，D14 时弹性酶 MV 小鼠的肺泡巨噬细胞过度表达 Gr1，单核细胞过度表达 CD62L 的趋势。在弹性蛋白酶诱导的肺气肿模型中，常规潮气量机械通气可能会导致肺中性粒细胞比例增加，并激活肺泡巨噬细胞和肺单核细胞。这种反应似乎仅在肺气肿模型出现潜在炎症（D14）时观察到，这反映在激活的肺泡巨噬细胞 CD11b 的存在上。
