Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
Injury. 2012 Aug;43(8):1257-63. doi: 10.1016/j.injury.2011.12.026. Epub 2012 Feb 14.
N-acetylcysteine (NAC) suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesised that NAC attenuates VILI. VILI was induced by mechanical ventilation with a tidal volume (Vt) of 15mlkg(-1) in isolated and perfused rat lung. NAC was administered in the perfusate prior to the onset of mechanical ventilation. A group ventilated with low Vt of 5mlkg(-1) served as control. Haemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined upon completion of the mechanical ventilation. There was an increase in lung permeability and lung weight gain after mechanical ventilation with high Vt, compared to low Vt. The levels of inflammatory cytokines including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; the concentrations of H(2)O(2) were higher in lung lavage fluids, and the expression of myeloperoxidase (MPO), JNK, P38, pAKT and caspase-3 in lung tissue was greater in the high Vt than in the low Vt group. The concentrations of glutathione (GSH) in lung tissue were higher in low Vt than those in high Vt. The administration of NAC increased GSH, attenuated ROS, cytokines, MPO, JNK, pAKT and caspase-3 and lung permeability associated with decreased activation of nuclear factor-κB. VILI is associated with inflammatory responses including the generation of ROS, cytokines and the activation of mitogen-activated protein kinase cascade. The administration of NAC attenuates the inflammatory responses, apoptosis and VILI in the isolated, perfused rat lung model.
N-乙酰半胱氨酸（NAC）可抑制活性氧（ROS）的产生，ROS 被认为与呼吸机所致肺损伤（VILI）有关。因此，我们假设 NAC 可以减轻 VILI。在离体灌注大鼠肺中，通过 15ml/kg 的潮气量（Vt）进行机械通气来诱导 VILI。在开始机械通气前，将 NAC 加入灌流液中。通气量为 5ml/kg 的低 Vt 组作为对照。完成机械通气后，测定血流动力学、肺损伤指数、炎症反应和凋亡途径的激活情况。与低 Vt 相比，高 Vt 机械通气后肺通透性增加，肺重量增加。炎症细胞因子包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和巨噬细胞炎症蛋白-2（MIP-2）的水平在肺灌洗液中升高；灌洗液中 H2O2 的浓度较高，肺组织中髓过氧化物酶（MPO）、JNK、P38、pAKT 和 caspase-3 的表达在高 Vt 组高于低 Vt 组。低 Vt 组肺组织中的谷胱甘肽（GSH）浓度高于高 Vt 组。NAC 的给药增加了 GSH，减轻了 ROS、细胞因子、MPO、JNK、pAKT 和 caspase-3，以及与核因子-κB 激活减少相关的肺通透性。VILI 与炎症反应有关，包括 ROS、细胞因子和丝裂原活化蛋白激酶级联的激活。NAC 的给药可减轻离体灌注大鼠肺模型中的炎症反应、细胞凋亡和 VILI。
