Mechanism and therapy of ventilator-induced lung injury

本研究旨在探讨呼吸机相关性肺损伤的发生机制及治疗方法。采用大潮气量(15mL/kg)机械通气法建立兔急性肺损伤模型(损伤组)。非损伤组按标准通气量(8m L/kg)进行机械通气。损伤组肺氧合功能和肺顺应性在机械通气开始后2小时下降。此外，血浆细胞因子(IL-6)水平升高。光镜检查显示高潮气量通气量可引起肺水肿和中性粒细胞渗入肺泡腔。气管内给予受损肺氟碳可减轻氧合、肺顺应性和组织损伤的加重，但不能抑制细胞因子的产生。第二项研究使用培养的肺泡上皮II型细胞(AEC-II)。剪切力作用2小时不改变AEC-II(A549)的构象，但增加IL-6和MCP-1mRNA的表达。氟碳处理可抑制切应力诱导的炎性细胞因子的mRNA表达。我们的研究表明，氟碳改善了体内肺损伤模型的氧合和病理变化，而氟碳的抗炎作用并不是其改善机制中的重要作用。

The aim of our study was to explore mechanism of ventilator-induced lung injury and seek its therapy. Acute lung injury was induced by high tidal volume ventilation (15 mL/kg) in rabbits (Injury Group). In Non-injury Group, the lungs were mechanically ventilated by standard volume (8 mL/kg). In Injury Group, oxygenation and lung compliance were decreased 2 hrs after the start of ventilation. Furthermore, plasma cytokine (IL-6) level was increased. Light microscopic examination showed that high tidal volume ventilation caused lung edema and infiltration of neutrophils into alveolar spaces. Intratracheal administration of fluorocarbon to the injured lungs attenuated aggravation of oxygenation, lung compliance, and histological damage, but failed to inhibit cytokine production. The second study used cultured alveolar epithelial type II cells (AEC-II). Shear stress for 2 hrs did not change conformation of AEC-II (A549), but increased expression of IL-6 and MCP-1 mRNA. Treatment of fluorocarbon inhibited shear stress-induced mRNA expression of the inflammatory cytokines. Our studies suggest that fluorocarbon improved oxygenation and pathological changes in in-vivo lung injury model, and attenuation of inflammation with fluorocarbon did not play an important role in the mechanism of improvement.