Gurkan Ozlem U, O'Donnell Christopher, Brower Roy, Ruckdeschel Emily, Becker Patrice M
Div. of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Rm. 4B74, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L710-8. doi: 10.1152/ajplung.00044.2003. Epub 2003 May 16.
Patients with acute respiratory distress syndrome are at increased risk for developing multiorgan system dysfunction. The goal of this study was to establish an in vivo murine model to assess the differential effects of ventilation-protective strategies on the development of acute lung injury and systemic organ inflammation. C57B/6 mice were randomized to mechanical ventilation (MV) with conventional, high (17 ml/kg) or protective, low (6 ml/kg) tidal volume (VT) after intratracheal hydrochloric acid or no intervention. Mean arterial pressure was continuously monitored during MV and did not differ between groups. After 4 h, lung injury was assessed by measurement of wet/dry lung weight, lung lavage protein concentration and cell count, and histology. Concentration of IL-6, TNF-alpha, VEGF, and VEGF receptor-2 (VEGFR2) was measured in lung, liver, kidney, and heart. Results were compared with control, spontaneously breathing mice. Lung injury and altered pulmonary cytokine expression were not detected after MV of healthy mice with low or high VT. Although MV did not significantly alter IL-6 or TNF-alpha in systemic organs, VEGF concentration significantly increased in liver and kidney. After acid aspiration, mice ventilated with high VT manifested lung injury and increased IL-6 and VEGFR2 in lung, liver, and kidney, whereas VEGF increased only in liver and kidney. MV with low VT after acid aspiration attenuated lung injury, both IL-6 and VEGFR2 expression in lung and systemic organs, and hepatic, but not renal, increased VEGF. Our data suggest that MV strategy has differential effects on systemic inflammatory changes and thus may selectively predispose to systemic organ dysfunction.
急性呼吸窘迫综合征患者发生多器官系统功能障碍的风险增加。本研究的目的是建立一种体内小鼠模型，以评估通气保护策略对急性肺损伤和全身器官炎症发展的不同影响。将C57B/6小鼠随机分为气管内注入盐酸后接受常规潮气量（17 ml/kg）或保护性低潮气量（6 ml/kg）机械通气（MV）组，或不进行干预组。在机械通气期间持续监测平均动脉压，各组之间无差异。4小时后，通过测量肺湿/干重、肺灌洗蛋白浓度和细胞计数以及组织学评估肺损伤。测量肺、肝、肾和心脏中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、血管内皮生长因子（VEGF）和VEGF受体-2（VEGFR2）的浓度。将结果与对照的自主呼吸小鼠进行比较。健康小鼠接受低或高潮气量机械通气后未检测到肺损伤和肺细胞因子表达改变。虽然机械通气未显著改变全身器官中的IL-6或TNF-α，但肝和肾中的VEGF浓度显著增加。酸吸入后，接受高潮气量通气的小鼠出现肺损伤，肺、肝和肾中的IL-6和VEGFR2增加，而VEGF仅在肝和肾中增加。酸吸入后接受低潮气量机械通气可减轻肺损伤、肺和全身器官中的IL-6和VEGFR2表达，以及肝脏（而非肾脏）中VEGF的增加。我们的数据表明，机械通气策略对全身炎症变化有不同影响，因此可能选择性地导致全身器官功能障碍。
