Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Casanova 143, 08036 Barcelona, Spain.
Eur Respir J. 2012 Oct;40(4):939-48. doi: 10.1183/09031936.00153211. Epub 2012 Mar 22.
Bone marrow-derived mesenchymal stem cells (MSCs) reduce acute lung injury in animals challenged by bleomycin or bacterial lipopolysaccaride. It is not known, however, whether MSCs protect from ventilator-induced lung injury (VILI). This study investigated whether MSCs have a potential role in preventing or modulating VILI in healthy rats subjected to high-volume ventilation. 24 Sprague-Dawley rats (250-300 g) were subjected to high-volume mechanical ventilation (25 mL·kg(-1)). MSCs (5 × 10(6)) were intravenously or intratracheally administered (n=8 each) 30 min before starting over-ventilation and eight rats were MSC-untreated. Spontaneously breathing anesthetised rats (n=8) served as controls. After 3 h of over-ventilation or control the animals were sacrificed and lung tissue and bronchoalveolar lavage fluid (BALF) were sampled for further analysis. When compared with controls, MSC-untreated over-ventilated rats exhibited typical VILI features. Lung oedema, histological lung injury index, concentrations of total protein, interleukin-1β, macrophage inflammatory protein-2 and number of neutrophils in BALF and vascular cell adhesion protein-1 in lung tissue significantly increased in over-ventilated rats. All these indices of VILI moved significantly towards normalisation in the rats treated with MSCs, whether intravenously or intratracheally. Both local and systemic pre-treatment with MSCs reduced VILI in a rat model.
骨髓间充质干细胞(MSCs)可减轻博来霉素或细菌脂多糖所致动物的急性肺损伤。然而,尚不清楚 MSCs 是否可预防呼吸机所致肺损伤(VILI)。本研究旨在探讨 MSCs 在高容量通气的健康大鼠中是否具有预防或调节 VILI 的作用。24 只 Sprague-Dawley 大鼠(250-300g)接受高容量机械通气(25ml·kg(-1))。在开始过度通气前 30 分钟,通过静脉内或气管内给予 MSCs(5×10(6)个)(每组各 8 只),并对 8 只大鼠不给予 MSC 治疗作为对照。8 只自主呼吸麻醉大鼠作为对照组。过度通气 3 小时或对照组动物被处死,采集肺组织和支气管肺泡灌洗液(BALF)用于进一步分析。与对照组相比,未给予 MSC 治疗的过度通气大鼠表现出典型的 VILI 特征。肺水肿、组织学肺损伤指数、总蛋白、白细胞介素-1β、巨噬细胞炎症蛋白-2 和 BALF 中性粒细胞数量以及肺组织血管细胞黏附蛋白-1浓度在过度通气大鼠中显著增加。在接受 MSCs 治疗的大鼠中,所有这些 VILI 指数均显著向正常化方向移动,无论是静脉内还是气管内给予 MSCs。在大鼠模型中,局部和全身给予 MSC 预处理可减轻 VILI。