Galli Thiago Tafarel, de Campos Elaine Cristina, do Nascimento Camargo Leandro, Fukuzaki Silvia, Dos Santos Tabata Marayama, Hamaguchi Sara Sumie Sobral, Bezerra Suellen Karoline Moreira, Silva Fabio José Alencar, Rezende Bianca Goulart, Dos Santos Lopes Fernanda Tenório Quirino, Olivo Clarice Rosa, Saraiva-Romanholo Beatriz Mangueira, Prado Carla Máximo, Leick Edna Aparecida, Bourotte Christine Laure Marie, Benseñor Isabela Judith Martins, Lotufo Paulo Andrade, Righetti Renato Fraga, Tibério Iolanda Fátima Lopes Calvo
Faculdade de Medicina (FMUSP), São Paulo, Brazil.
Hospital Sírio-Libanês, São Paulo, Brazil.
Sci Rep. 2024 Apr 21;14(1):9134. doi: 10.1038/s41598-024-59573-8.
Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-β, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes.
长期接触铁粉和其他矿物粉尘会威胁个人健康,尤其是慢性阻塞性肺疾病(COPD)患者。本研究的目的是确定巴西两个不同采矿中心的环境金属粉尘暴露如何影响健康小鼠和经弹性蛋白酶处理的小鼠的肺力学、炎症、重塑和氧化应激反应。本研究将72只雄性C57Bl/6小鼠分为两组,即夏季组和冬季组。这些组进一步分为六组:对照组,未暴露(SAL);未暴露,给予弹性蛋白酶(ELA);暴露于一家矿业公司的金属粉末(SAL-L1和ELA-L1);以及暴露于距离该矿业公司三英里处的地点(SAL-L2和ELA-L2),为期四周。在实验方案的第29天,研究人员评估了肺力学、支气管肺泡灌洗液(BALF)、炎症、重塑、氧化应激、巨噬细胞铁含量和肺泡壁改变(平均线性截距-Lm)。与SAL组相比,ELA、ELA-L1和ELA-L2组的Lm增加(p < 0.05)。与其他组相比,ELA-L1和ELA-L2组的细胞总数和巨噬细胞数量增加(p < 0.05)。与ELA组和SAL组相比,暴露组(ELA-L1、ELA-L2、SAL-L1和SAL-L2)的IL-1β、IL-6、IL-10、IL-17、TNF-α、中性粒细胞弹性蛋白酶、TIMP-1、MMP-9、MMP-12、TGF-β、胶原纤维、MUC5AC、iNOS、Gp91phox、NFkB和铁阳性巨噬细胞的表达增加(p < 0.05)。尽管我们在所有组中未发现肺力学方面的差异,但炎症重塑、氧化应激和NFkB与弹性、肺组织阻力和铁阳性巨噬细胞之间存在低至中度的相关性(p < 0.05)。通过评估肺泡巨噬细胞和空气中的铁证实,环境铁暴露加剧了暴露小鼠(无论有无肺气肿)的炎症,引发了重塑,并诱导了氧化应激反应。iNOS、Gp91phox和NFkB途径的激活在这些变化中起作用。