【作者】 李经华；

【导师】 颜亮； 孙婵；

【作者基本信息】 暨南大学 ， 病理生理学， 2005， 硕士

【摘要】 目的: 急性肺损伤（acute lung injury,ALI）/急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）是临床常见的危重病症,死亡率很高,以多种炎症细胞激活、细胞因子大量释放为特征的肺部过度炎症反应是其发生的重要机制,在治疗方面亟待重大突破。部分液体通气（partial liquid ventilation,PLV）是以液体氟碳化合物（perfluorocarbon,PFC）为通气媒介的一种新型有效的液体换气技术。研究表明,液体通气可以显著改善肺气体交换、提高肺顺应性,提高实验动物的生存率,在治疗ALI及ARDS中显示出独特优势。推测PLV可能具有抗炎效应。本实验采用经典的肺灌洗诱导的急性肺损伤家猪模型,实施PLV,观测肺损伤指标的变化,探讨其抗炎效应及其机制,为临床应用提供理论依据。 方法: 一、动物实验 16只体重为22～25kg的健康家猪,随机分为常规机械通气（mechanical ventilation,MV）（n=8）和PLV组（n=8）,记录ALl前各肺气体交换和血液动力学参数为基础值（Baseline）。ALI模型的建立参照Lachmann介绍的肺灌洗（lung lavage）方法,即将动物气管内灌入37℃、40mL/kg生理盐水,停留数秒后放出生理盐水,5分钟后重复上述操作,于第二次肺灌洗后5分钟行血气分析直至PaO₂<100mmHg（FiO₂=1.0）,并维持1h,此时为ALI。MV组用呼吸机行常规机械通气4h;PLV组经气管内注入30mL/kg氧合的液体氟碳化合物FC-77,并与MV组以同样的呼吸参数行机械通气4h,期间经气管导管连接接头处持续滴入FC-77,以弥补其蒸发损失量。于ALl时及其后1h、2h、3h和4h分别记录两组动物肺气体交换和血液动力学参数。 二、标本的采集及各损伤指标的检测 动物实验结束后,留取静脉血、支气管肺泡灌洗液、肺组织匀浆测定MDA、SOD、TNF-α、IFN-γ及白细胞渗漏情况,并制备肺脏光镜和电镜标本观察组织病理学变化。 结果: 动物实验结果显示,PLV组动物的动脉血氧分压（PaO₂）及动脉血氧饱和度（SaO₂）等明显高于MV组,肺泡动脉氧分压差（AaDO₂）及肺内分流（Qs/Qt）等明显低于MV组;两组动物的循环参数如心率（HR）、平均动脉压（MAP）、更多还原

【Abstract】 OBJECTIVE:Acute lung injury (ALI) / acute respiratory distress syndrome(ARDS) continue to be clinical serious pathological processes with high mortality. It’s critical component is the excessive lung inflammatory response induced by an elevated level of cytokines and activated phlogistic cells. Prompt and significant solutions are required. Partial liquid ventilation (PLV) has showed its advantage in the therapy of ALI/ARDS as an effective new pattern of ventilation with liquid respiratory medium of perfluorocarbon (PFC). Most animal models of acute lung injury have demonstrated that PLV improve oxygenation, lung acclimation, survival and anti-inflammatory effect. In our research, we investigate the anti-inflammatory effect of PLV with PFC in the piglets with lung lavage-induced acute lung injury, aim to provide warrant for clinical therapy of acute lung injury. METHODS:16 healthy piglets weighting 22-25 kg were randomly divided into mechanical ventilation (MV) group (n=8) and PLV group (n=8). The animals were tracheotomized and mechanically ventilated with oxygen (FiO2=1.0). The parameters of gas exchange and hemodynamics were measured before lung lavage as Baseline. Acute lung injury (ALI) were induced by lung lavage according to Lachmann. All piglets were surfactant-depleted by lung lavage using 37 ℃, 40 mL/kg of 9 g/L NaCl until PaO2<100 mmHg (FiO2=1.0) for one hour. Conventional mechanical ventilation was administered in MV group. In PLV group the animals received doses of 30 mL/kg perfluorocarbon FC-77 and mechanical ventilation was administered for 4 h. FC-77 was continued dropping via tracheal tube to redeem the evaporation during therapy. The parameters of gas exchange and hemodynamics were measured at moment of ALI establishment and the time points of 1 h, 2 h, 3 h, 4 h after ALI in both groups. At the end of animal experiment, samples of the venous blood, bronchoalveolar lavage fluid and lung tissue were obtained for detecting the contents of MDA SOD TNF-α IFN-γ and infiltration of PMN. The tissue sections were also prepared for the observationof lung injury under the light and electronic microscopes. RESULTS:After PFC instillation, PaO2 and SaO2 in PLV group were significantly higher, AaDO2 and Qs/Qt significantly reduced than those in MV group. Mean pulmonary artery pressure(MPAP) in MV group significantly increased than Baseline; MPAM, PCWP and other hemodynamics had no significant difference compared with MV group.Histopathologic findings showed that lung edema and hemorrhage were observed in MV group under light microscope. The pulmonary surfactant layer was discontinuous, lamellar bodies and plasmosomes in type II alveolar cells became vacuolization. The above impairments were slighter in PLV group. The W/G and PPI, the content of MDA and activity of MPO in PLV group were significantly lower than those in MV group. The content of TNF-a and IFN-y in plasma and lung tissue in PLV group were significantly lower than those in MV group. No significantly difference of NF-kB between the two groups was observed. CONCLUSION:Our data indicate that PLV protect lung from the excessive lung inflammatory response in ALL The mechanisms of protection might be associated with the decrease in PMN congregation, Hpid oxygenation damage and cytokines release.更多还原