Prado Carla Máximo, Righetti Renato Fraga, Lopes Fernanda Degobbi Tenorio Quirino Dos Santos, Leick Edna Aparecida, Arantes-Costa Fernanda Magalhães, de Almeida Francine Maria, Saldiva Paulo Hilário Nascimento, Mauad Thais, Tibério Iolanda de Fátima Lopes Calvo, Martins Mílton de Arruda
Department of Bioscience, Federal University of Sao Paulo, Santos, Rua Silva Jardim 136, 11015-020 Santos, SP, Brazil.
Faculdade de Medicina FMUSP, Universidade de São Paulo, Av. Dr. Arnaldo 455, Sala 1210, 01246-903 São Paulo, SP, Brazil.
Pulm Med. 2019 Mar 11;2019:4781528. doi: 10.1155/2019/4781528. eCollection 2019.
. The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and acute lung damage is well known. However, the mechanism involved in the effects of repeated exposures of PM in the lung injury is poorly documented. This study tested the hypotheses that chronic nasal instillation of residual oil fly ash (ROFA) induced not only distal lung and airway inflammation but also remodeling. In addition, we evaluated the effects of inducible nitric oxide inhibition in these responses. For this purpose, airway and lung parenchyma were evaluated by quantitative analysis of collagen and elastic fibers, immunohistochemistry for macrophages, neutrophils, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and alveolar septa 8-iso prostaglandin F2 (8-iso-PGF-2) detection. Anesthetized i (airway resistance, elastance, H, G, and Raw) respiratory mechanics were also analyzed. C57BL6 mice received daily 60ul of ROFA (intranasal) for five (ROFA-5d) or fifteen days (ROFA-15d). Controls have received saline (SAL). Part of the animals has received 1400W (SAL+1400W and ROFA-15d+1400W), an iNOS inhibitor, for four days before the end of the protocol. A marked neutrophil and macrophage infiltration and an increase in the iNOS, nNOS, and 8-iso-PGF2 expression was observed in peribronchiolar and alveolar wall both in ROFA-5d and in ROFA-15d groups. There was an increment of the collagen and elastic fibers in alveolar and airway walls in ROFA-15d group. The iNOS inhibition reduced all alterations induced by ROFA, except for the 8-iso-PGF2 expression. In conclusion, repeated particulate matter exposures induce extracellular matrix remodeling of airway and alveolar walls, which could contribute to the pulmonary mechanical changes observed. The mechanism involved is, at least, dependent on the inducible nitric oxide activation.
肺部暴露于环境颗粒物（PM）与急性肺损伤之间的流行病学关联已为人熟知。然而，关于PM反复暴露在肺损伤中所涉及的机制，相关文献记载较少。本研究检验了以下假设：慢性经鼻滴注残留油飞灰（ROFA）不仅会引发远端肺和气道炎症，还会导致重塑。此外，我们评估了诱导型一氧化氮抑制对这些反应的影响。为此，通过对胶原蛋白和弹性纤维进行定量分析、对巨噬细胞、中性粒细胞、诱导型一氧化氮合酶（iNOS）、神经元型一氧化氮合酶（nNOS）进行免疫组织化学检测以及检测肺泡隔8-异前列腺素F2（8-异-PGF-2），来评估气道和肺实质。还分析了麻醉状态下的i（气道阻力、弹性、H、G和气道阻力）呼吸力学。C57BL6小鼠每天经鼻接受60微升ROFA，持续五天（ROFA-5d）或十五天（ROFA-15d）。对照组接受生理盐水（SAL）。部分动物在实验方案结束前四天接受了1400W（SAL+1400W和ROFA-15d+1400W），一种iNOS抑制剂。在ROFA-5d组和ROFA-15d组的细支气管周围和肺泡壁均观察到明显的中性粒细胞和巨噬细胞浸润以及iNOS、nNOS和8-异-PGF2表达增加。ROFA-15d组肺泡和气道壁中的胶原蛋白和弹性纤维有所增加。iNOS抑制减少了ROFA诱导的所有改变，但8-异-PGF2表达除外。总之，颗粒物反复暴露会导致气道和肺泡壁的细胞外基质重塑，这可能是观察到的肺部力学变化的原因。所涉及的机制至少依赖于诱导型一氧化氮的激活。
