Research on mechanism of ventilator induced lung injury

常规机械通气（CMV）与间歇性正压启动和加重肺损伤。高频振荡（HFO）已被公认为是一种有效的治疗策略，以减少肺损伤的呼吸支持。1）肺泡上皮细胞TNF-α的表达在肺表面活性物质耗竭模型中，CMV机械通气可增加肺泡上皮细胞TNF-α的表达。我们比较了HFO和CMV通气后肺泡上皮细胞中TNF-α的表达。我们发现，CMV通气诱导肺上皮细胞TNF-α的弥漫性表达，但在表面活性剂耗竭模型中，HFO的TNF-α表达最小。2）表面活性剂耗竭兔肺机械通气期间IL-8的产生我们测量了两种通气方法后灌洗液和肺中IL-8的水平。CMV组灌洗液和肺组织中IL-8含量均显著高于HFO组。CMV组肺泡上皮细胞、肺泡巨噬细胞及内皮细胞免疫组化染色强。而HFO组肺细胞中的信号较弱。结论：IL-8的释放可能在肺损伤中起重要作用。3）NF-κ B的活化HFO组肺组织NF-κ B活性较低。CMV组肺组织NF-κ B活性明显升高。去除肺泡细胞后，HFO 4小时肺组织NF-κ B活性较CMV 4小时肺组织略有升高。我们认为高水平NF κ B的来源可能是浸润肺泡的中性粒细胞。

Conventional mechanical ventilation (CMV) with intermittent positive pressure initiates and exacerbates lung injury. High-frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury in respiratory support. We did following studies to clarify the mechanism of lung injury induced by CMV,1) The expression of TNF-alpha in the alveolar epithelial cells in surfactant-depleted lung model In surfactant-depleted lung, mechanical ventilation with CMV increased production of TNF-alpha in air space. We compared the expression of TNF-alpha in alveolar epithelial cells after ventilation with HFO and CMV. We showed that ventilation with CMV induces diffuse pulmonary epithelial expression of TNF-alpha but the expression of TNF-alpha was minimal with HFO in surfactant-depleted model.2) Production of IL-8 during mechanical ventilation in a surfactant-depleted rabbit lungWe measured the level of IL-8 in the lavage fluid and in the lung after both ventilation methods. The values of IL-8 in lavage fluid and in the lung were significantly greater in CMV group than in HFO group. Immunohistochemistry of CMV group showed alveolar epithelial cells, alveolar macrophages and endothelial cells were strongly stained. In turn, the signals were weaker in lung cells of HFO group. We concluded that release of IL-8 might have an important role in lung injury in this model.3) Activation of NF-kappaBIn lungs of HFOgroup, NF-kappaB activity was slight. In contrast, the activity of NF kappaB was increased markedly in the lung of CMV group. After removal of alveolar cells, the level of NF kappaB activity slightly increased in lungs of 4hr HFO compared with that of 4hr CMV. We thought that the source of the high level of NF kappaB might have been PMNs that had infiltrated the alveoli.