Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit
Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit
复制标题
DOI：
10.1371/journal.pone.0158799
复制
发表时间：
2016-07-08
期刊：
影响因子：
3.7
通讯作者：
Charles, Pierre-Emmanuel
中科院分区：
文献类型：
--
作者：
Barbar, Saber-Davide;Pauchard, Laure-Anne;Charles, Pierre-Emmanuel
呼吸机相关性肺炎（VAP）在机械通气（MV）期间很常见。除了对粘液纤毛清除有明显的有害影响外，MV 还可以通过 Toll 样受体 (TLR) 上调，将宿主免疫反应转向促炎模式。我们在金黄色葡萄球菌 VAP 兔模型中测试了这一假设。自发呼吸 (SB) 或 MV 兔子（分别为 n = 13 和 17）中，肺炎是由金黄色葡萄球菌气道激发引起的。在金黄色葡萄球菌攻击后 8 小时和 24 小时进行有关肺部和全身细菌负荷以及炎症反应的肺炎评估。此外，用 TLR2 激动剂或热灭活的金黄色葡萄球菌对取自 SB 或 MV 兔（分别为 7 只和 5 只）的全血进行离体刺激。数据表示为平均值+/-标准差。感染 8 小时后，MV 动物的肺损伤更严重（1.40 +/- 0.33 对比 2.40 +/- 0.55，p = 0.007），同时细菌浓度更高（6.13 +/- 0.63 对比 4.96 +/- 1.31 菌落形成单位/克，p = 0.002）。 MV 动物中白细胞介素 (IL)-8 和肿瘤坏死因子 (TNF)-α 血清浓度达到较高水平 (p = 0.010)。如果用 TLR2 激动剂或热灭活的金黄色葡萄球菌刺激，从 MV 动物获得的全血会释放大量细胞因子（例如 TNF-α：1656 +/- 166 与 1005 +/- 89；p = 0.014）。此外，MV 诱导肺和脾组织中 TLR2 过度表达。 MV 可能通过 TLR2 过度表达加速组织损伤，损害肺部细菌清除，并促进全身炎症反应。
Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean +/- standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40 +/- 0.33 versus [vs] 2.40 +/- 0.55, p = 0.007), along with greater bacterial concentrations (6.13 +/- 0.63 vs. 4.96 +/- 1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha serum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-alpha: 1656 +/- 166 vs. 1005 +/- 89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression.