新型无创仪器雾化吸入肺表面活性物质联合地塞米松对急性肺损伤大鼠的治疗作用。
Therapeutic effects of inhaling aerosolized surfactant alone or with dexamethasone generated by a novel noninvasive apparatus on acute lung injury in rats.
机构信息
Department of Pathophysiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.
出版信息
J Trauma Acute Care Surg. 2012 Nov;73(5):1114-20. doi: 10.1097/TA.0b013e318265cbe9.
BACKGROUND
Pulmonary surfactant (PS) administration has been attempted for the treatment of adults with acute lung injury (ALI)/adult respiratory distress syndrome. Aerosolized surfactants inhaled by spontaneous breathing may be an effective method of surfactant-based therapies. Using a noninvasive apparatus, we evaluated the therapeutic effects of aerosolized PS alone or together with dexamethasone (Dex) on a rat model of ALI.
METHODS
Severe ALI was induced by intravenous injection of 20% oleic acid (0.2 mL/kg) into adult Sprague-Dawley rats. Animals were divided into eight groups: sham (n = 10); model (injury only, n = 10); normal saline (NS) aerosol driven by compressed air (air-NS, n = 13); PS aerosol driven by compressed air (air-PS, n = 13); NS aerosol driven by O2 (O2-NS, n = 13); PS aerosol driven by O2 (O2-PS, n = 13); Dex aerosol driven by O2 (O2-Dex, n = 13); and PS and Dex aerosol driven by O2 (O2-PS-Dex, n = 13). Blood gases, breathing rate, lung index, total protein, and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, interleukin 6) in the bronchoalveolar lavage fluid (BALF), and lung histology were examined.
RESULTS
Animals treated with air-PS for 20 minutes had significantly improved lung function, reduced pulmonary edema, decreased concentration of total protein and proinflammatory cytokines in BALF, ameliorated lung injury, and improved animal survival. In the O2-PS group, the breathing rates and lung injury scores were significantly lower than that of the air-PS group. In the O2-PS-Dex group, lung edema, total protein, and inflammatory cytokines in BALF were significantly reduced in comparison with the O2-PS group.
CONCLUSION
Inhalation of aerosolized PS generated by the noninvasive apparatus could significantly reduce lung injury, while using oxygen line available in the clinical wards to generate PS aerosol is more convenient and adds further benefits. This method can also be used to deliver Dex and other therapeutic agents to ameliorate lung injury.
背景
肺表面活性物质（PS）已被尝试用于治疗成人急性肺损伤（ALI）/成人呼吸窘迫综合征。通过自主呼吸吸入雾化的表面活性剂可能是一种有效的表面活性剂治疗方法。我们使用一种非侵入性装置，评估了单独使用雾化 PS 或联合地塞米松（Dex）治疗 ALI 大鼠模型的治疗效果。
方法
通过静脉注射 20%油酸（0.2 mL/kg）诱导成年 Sprague-Dawley 大鼠发生严重 ALI。动物分为八组：假手术组（n=10）；模型组（仅损伤，n=10）；空气驱动生理盐水（air-NS，n=13）雾化；空气驱动 PS（air-PS，n=13）雾化；氧气驱动生理盐水（O2-NS，n=13）雾化；氧气驱动 PS（O2-PS，n=13）雾化；氧气驱动地塞米松（O2-Dex，n=13）雾化；氧气驱动 PS 和地塞米松（O2-PS-Dex，n=13）雾化。检测血气、呼吸频率、肺指数、支气管肺泡灌洗液（BALF）中的总蛋白和促炎细胞因子（肿瘤坏死因子-α、白细胞介素 1β、白细胞介素 6）以及肺组织学变化。
结果
空气-PS 治疗 20 分钟的动物肺功能显著改善，肺水肿减轻，BALF 中总蛋白和促炎细胞因子浓度降低，肺损伤改善，动物存活率提高。与空气-PS 组相比，O2-PS 组呼吸频率和肺损伤评分显著降低。与 O2-PS 组相比，O2-PS-Dex 组 BALF 中的肺水肿、总蛋白和炎症细胞因子明显减少。
结论
非侵入性装置产生的雾化 PS 吸入可显著减轻肺损伤，而使用临床病房中现有的氧气线生成 PS 气雾剂更为方便，并带来额外的益处。该方法还可用于输送地塞米松和其他治疗药物以改善肺损伤。
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