Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury

Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury
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DOI:
10.1183/09031936.00153211
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发表时间:
2012-10-01
影响因子:
24.3
通讯作者:
Farre, Ramon
Farre, Ramon
中科院分区:
医学1区
文献类型:
--
作者:
Chimenti, Laura;Luque, Tomas;Farre, Ramon

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骨髓来源的间充质干细胞(MSCs)可减轻博来霉素或细菌脂多糖引起的动物急性肺损伤。然而,目前尚不清楚间充质干细胞是否能保护呼吸机诱导的肺损伤(VILI)。本研究探讨了MSCs是否在大容量通气的健康大鼠中具有预防或调节VILI的潜在作用Sprague-Dawley大鼠(250-300 g)给予大容量机械通气(25 mL.kg(-1))。在开始过度通气前30分钟静脉或气管内给予MSCs (5 × 10(6))(各n=8), 8只大鼠未给予MSCs治疗。自主呼吸麻醉大鼠(n=8)作为对照组。在过度通气或对照组3 h后处死动物,取肺组织和支气管肺泡灌洗液(BALF)进一步分析。与对照组相比,未经msc处理的过度通气大鼠表现出典型的VILI特征。过度通气大鼠肺水肿、肺组织损伤指数、肺组织总蛋白、白细胞介素-1 β、巨噬细胞炎症蛋白-2浓度及BALF、血管细胞粘附蛋白-1中性粒细胞数量显著升高。无论是静脉注射还是气管内注射MSCs,大鼠的VILI的所有这些指数都明显趋于正常化。在大鼠模型中,局部和全身MSCs预处理均可降低VILI。
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 x 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-1 beta, 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.