Center of Emergency & Intensive Care Unit .
Inhal Toxicol. 2014 Feb;26(3):185-92. doi: 10.3109/08958378.2013.872213.
Animals exposed to phosgene (Psg) result in acute lung injury (ALI). We have recently reported that angiopoietin-1 (Ang1) reduces inflammation and vascular hyperpermeability in ALI animals. In this study, we examined whether the beneficial effects of adenovirus-delivered Ang1 (Ad/Ang1) on inflammatory responses in Psg-induced ALI rats are due to the suppression of the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways, which play crucial roles in inflammatory responses in ALI. We demonstrated that Psg increased Ang2 and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4 (IL-4), IL-6, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid of ALI rats, determined by ELISA. Ang1 inhibits pro-inflammatory mediators (TNF-α, IL-6 and IL-8) and has no effect on anti-inflammatory mediators (IL-4 and IL-10). Furthermore, the inhibitory action of Ang1 was mediated by the suppression of the NF-κB and p38 MAPK pathways, leading to the attenuation of inflammatory responses of ALI. Thus, Ad/Ang1 may provide a useful tool for the effective treatment in Psg-induced ALI.
动物暴露于光气（Psg）会导致急性肺损伤（ALI）。我们最近报道，血管生成素-1（Ang1）可减轻 ALI 动物的炎症和血管通透性增加。在这项研究中，我们研究了腺病毒递送的 Ang1（Ad/Ang1）对 Psg 诱导的 ALI 大鼠炎症反应的有益作用是否归因于核因子-κB（NF-κB）和丝裂原活化蛋白激酶（p38 MAPK）途径的抑制，这些途径在 ALI 中的炎症反应中起着至关重要的作用。我们证明，ELISA 测定表明，Psg 增加了 ALI 大鼠血清和支气管肺泡灌洗液中 Ang2 和炎症细胞因子，如肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-4（IL-4）、IL-6、IL-8 和 IL-10。Ang1 抑制促炎介质（TNF-α、IL-6 和 IL-8），对抗炎介质（IL-4 和 IL-10）没有影响。此外，Ang1 的抑制作用是通过抑制 NF-κB 和 p38 MAPK 途径介导的，从而减轻 ALI 的炎症反应。因此，Ad/Ang1 可能为 Psg 诱导的 ALI 的有效治疗提供了有用的工具。
