摘要
目的:本研究旨在不同潮气量和呼气正末压(PEEP)的肺保护通气策略对慢性阻塞性肺疾病COPD模型大鼠呼吸功能和血液动力学的影响.方法:采用烟熏和气管内滴注脂多糖(LPS)法构建COPD大鼠模型.将大鼠随机分为9 组,每组10 只:对照组和COPD组仅给予气管插管,不给予机械通气;L+P0 组、L+P3 组、L+P5 组、L+P10 组在气管插管后分别给予 6mL/kg 小潮气量和 0cm H2O、3cm H2O、5cm H2O、10cm H2O PEEP 的机械通气120min;H+P0 组、H+P3 组、H+P5 组、H+P10 组在气管插管后分别给予20mL/kg大潮气量和 0cm H2O、3cm H2O、5cm H2O、10cm H2O PEEP 的机械通气 120min.分别在小动物无创呼吸功能监测系统和血气分析仪中测量呼吸功能和血液动力学指标.采用酶联免疫吸附实验检测肺组织和肺泡灌洗液(BALF)中炎症介质的水平.结果:与对照组相比,COPD 组大鼠呼吸功能指标和PaO2 均明显降低(P<0.05);与COPD组相比,L+P0 组、L+P3 组、L+P5 组呼吸功能指标和PaO2 均明显升高(P<0.05),而L+P10 组、H+P0 组、H+P3 组、H+P5 组和H+P10 组均明显降低(P<0.05);L+P5 组呼吸功能指标和PaO2 均明显高于 L+P0 组和 L+P3 组(P<0.05);与 L+P5 组相比,L+P10 组、H+P0 组、H+P3 组、H+P5 组和H+P10 组呼吸功能指标和PaO2 均明显降低(P<0.05).与对照组相比,COPD组肺组织和BALF中IL-8 和TNF-α水平显著升高,而IL-10 水平显著降低(P<0.05);与COPD组相比,L+P0 组、L+P3 组、L+P5 组 IL-8 和 TNF-α 水平显著降低、IL-10 水平显著升高(P<0.05),而L+P10 组、H+P0 组、H+P3 组、H+P5 组和H+P10 组IL-8 和 TNF-α 水平显著升高、IL-10 水平显著降低(P<0.05);L+P5 组肺组织中IL-8 和 TNF-α 水平显著低于 L+P0 组和 L+P3 组,而 IL-10水平显著高于L+P0 组和L+P3 组(P<0.05);与 L+P5 组相比,L+P10 组、H+P0 组、H+P3 组、H+P5 组和H+P10 组IL-8 和TNF-α水平显著升高,而IL-10 水平显著降低(P<0.05).结论:小潮气量与较高PEEP(如5cm H2O PEEP)的肺保护通气策略能够减轻COPD大鼠的肺部炎症和肺损伤,改善COPD患者呼吸功能和血液动力学.
Abstract
Objective:To investigate the effects of different tidal volumes and positive end-expiratory pressure(PEEP)lung protective ventilation strategies on respiratory function and hemodynamics in COPD rat models.Methods:COPD rat models were established by smoke inhalation and intratracheal administration of lipopolysaccharide(LPS).Rats were randomly divided into 9 groups(10 rats per group):control and COPD groups received tracheal intubation only without mechanical ventilation;L+P0 group,L+P3 group,L+P5 group,and L+P10 group received mechanical ventilation with 6 ml/kg tidal volume and 0 cm H2O,3 cm H2O,5 cm H2O,and 10 cm H2O PEEP,respectively,for 120 min after tracheal intubation;H+P0 group,H+P3 group,H+P5 group,and H+P10 group received mechanical ventilation with 20 ml/kg tidal volume and 0 cm H2O,3 cm H2O,5 cm H2O,and 10 cm H2O PEEP,respectively,for 120 min after tracheal intuba-tion.Respiratory function and hemodynamic parameters were measured using a small animal non-invasive re-spiratory function monitoring system and blood gas analyzer.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory mediators in lung tissue and bronchoalveolar lavage fluid(BALF).Results:Compared with the control group,COPD rats showed significantly decreased respiratory function parameters and PaO2(P<0.05);compared with the COPD group,L+P0 group,L+P3 group,and L+P5 group showed significantly increased respiratory function parameters and PaO2(P<0.05),while L+P10 group,H+P0 group,H+P3 group,H+P5 group,and H+P10 group showed significantly decreased respiratory function parameters and PaO2(P<0.05);L+P5 group showed significantly higher respiratory function parame-ters and PaO2 than L+P0 group and L+P3 group(P<0.05);compared with L+P5 group,L+P10 group,H+P0 group,H+P3 group,H+P5 group,and H+P10 group showed significantly decreased respiratory function parameters and PaO2(P<0.05).Compared with the control group,COPD rats showed significantly increased levels of IL-8 and TNF-α in lung tissue and BALF,while IL-10 levels were significantly decreased(P<0.05);compared with the COPD group,L+P0 group,L+P3 group,and L+P5 group showed significantly de-creased levels of IL-8 and TNF-α and significantly increased levels of IL-10(P<0.05),while L+P10 group,H+P0 group,H+P3 group,H+P5 group,and H+P10 group showed significantly increased levels of IL-8 and TNF-α and significantly decreased levels of IL-10(P<0.05);L+P5 group showed significantly lower levels of IL-8 and TNF-α in lung tissue and significantly higher levels of IL-10 than L+P0 group and L+P3 group(P<0.05);compared with L+P5 group,L+P10 group,H+P0 group,H+P3 group,H+P5 group,and H+P10 group showed significantly increased levels of IL-8 and TNF-α and significantly decreased levels of IL-10(P<0.05).Conclusion:Lung protective ventilation strategies with low tidal volume and high-er PEEP(such as 5 cm H2O PEEP)can alleviate lung inflammation and lung injury in COPD rats,improve respiratory function and hemodynamics in COPD patients.