Department of Physiology & Pharmacology, Western University, London, Ontario, Canada.
BMC Pulm Med. 2013 Nov 20;13:67. doi: 10.1186/1471-2466-13-67.
Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.
Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).
For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.
The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.
机械通气（MV）是急性肺损伤（ALI）的重要支持性治疗方法；但它也会导致全身炎症。由于肺表面活性物质具有抗炎特性，因此本研究的目的是研究外源性表面活性物质给药对通气引起的全身炎症的影响。
将小鼠随机分为接受气管内滴注天然外源性表面活性剂制剂（bLES，50mg/kg）或不治疗作为对照。然后使用分离和灌流的小鼠肺（IPML）装置进行 MV。该模型允许在 MV 期间进行肺灌注。在实验 1 中，仅对小鼠进行机械通气（潮气量=20mL/kg，2 小时）。在实验 2 中，在应用外源性表面活性剂和通气（潮气量=5mL/kg，2 小时）前 4 小时，将盐酸或空气气管内滴注。
对于这两个实验，与对照组相比，外源性表面活性剂给药导致处理组的总表面活性物质和功能表面活性物质增加。与未治疗的对照组相比，仅接受 MV 的外源性表面活性剂给药的小鼠的吸气峰压（PIP）、肺 IL-6 水平和灌流液炎症的发展没有受到影响。与空气滴注对照组相比，接受常规 MV 的酸损伤小鼠显示出更高的 PIP、肺 IL-6 和蛋白水平以及更大的灌流液炎症。外源性表面活性剂的滴注并没有影响肺损伤的发展。此外，外源性表面活性剂不能有效地降低灌流液中炎症细胞因子的浓度。
数据表明，外源性表面活性剂在我们的模型中不能减轻通气引起的全身炎症。未来的研究将集中于改变表面活性剂的组成以提高其免疫调节活性。
