Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niterói, Brazil.
Front Immunol. 2019 May 29;10:1215. doi: 10.3389/fimmu.2019.01215. eCollection 2019.
Obese patients are at higher risk of developing acute respiratory distress syndrome (ARDS); however, their survival rates are also higher compared to those of similarly ill non-obese patients. We hypothesized that obesity would not only prevent lung inflammation, but also reduce remodeling in moderate endotoxin-induced acute lung injury (ALI). Obesity was induced by early postnatal overfeeding in Wistar rats in which the litter size was reduced to 3 pups/litter (Obese, = 18); Control animals ( = 18) were obtained from unculled litters. On postnatal day 150, Control, and Obese animals randomly received lipopolysaccharide (ALI) or saline (SAL) intratracheally. After 24 h, echocardiography, lung function and morphometry, and biological markers in lung tissue were evaluated. Additionally, mediator expression in neutrophils and macrophages obtained from blood and bronchoalveolar lavage fluid (BALF) was analyzed. Compared to Control-SAL animals, Control-ALI rats showed no changes in echocardiographic parameters, increased lung elastance and resistance, higher monocyte phagocytic capacity, collagen fiber content, myeloperoxidase (MPO) activity, and levels of interleukin (IL-6), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and type III (PCIII), and I (PCI) procollagen in lung tissue, as well as increased expressions of TNF-α and monocyte chemoattractant protein (MCP)-1 in blood and BALF neutrophils. Monocyte (blood) and macrophage (adipose tissue) phagocytic capacities were lower in Obese-ALI compared to Control-ALI animals, and Obese animals exhibited reduced neutrophil migration compared to Control. Obese-ALI animals, compared to Obese-SAL, exhibited increased interventricular septum thickness ( = 0.003) and posterior wall thickness ( = 0.003) and decreased pulmonary acceleration time to pulmonary ejection time ratio ( = 0.005); no changes in lung mechanics, IL-6, TNF-α, TGF-β, PCIII, and PCI in lung tissue; increased IL-10 levels in lung homogenate ( = 0.007); reduced MCP-1 expression in blood neutrophils ( = 0.009); decreased TNF-α expression in blood ( = 0.02) and BALF ( = 0.008) neutrophils; and increased IL-10 expression in monocytes ( = 0.004). In conclusion, after endotoxin challenge, obese rats showed less deterioration of lung function, secondary to anti-inflammatory and anti-fibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.
肥胖患者发生急性呼吸窘迫综合征（ARDS）的风险更高；然而，与同样患病的非肥胖患者相比，他们的存活率也更高。我们假设肥胖不仅可以预防肺部炎症，还可以减轻中等程度内毒素诱导的急性肺损伤（ALI）中的重塑。Wistar 大鼠通过产后早期过度喂养诱导肥胖，将每窝幼仔数量减少到 3 只/窝（肥胖，n = 18）；从未减少的窝中获得对照动物（n = 18）。在产后第 150 天，对照和肥胖动物随机接受气管内脂多糖（ALI）或生理盐水（SAL）。24 小时后，评估心脏超声、肺功能和形态计量学以及肺组织中的生物标志物。此外，还分析了来自血液和支气管肺泡灌洗液（BALF）的中性粒细胞和巨噬细胞中的介质表达。与对照-SAL 动物相比，对照-ALI 大鼠的心脏超声参数没有变化，肺弹性阻力增加，单核细胞吞噬能力增加，胶原纤维含量增加，髓过氧化物酶（MPO）活性增加，白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β和 III 型（PCIII）和 I 型（PCI）前胶原在肺组织中的水平增加，血液和 BALF 中性粒细胞中的 TNF-α和单核细胞趋化蛋白（MCP）-1表达增加。与对照-ALI 动物相比，肥胖-ALI 动物的单核细胞（血液）和巨噬细胞（脂肪组织）吞噬能力较低，肥胖动物的中性粒细胞迁移减少。与肥胖-SAL 相比，肥胖-ALI 动物的室间隔厚度（ = 0.003）和后壁厚度（ = 0.003）增加，肺射血时间与肺动脉加速时间比值（ = 0.005）降低；肺组织中肺力学、IL-6、TNF-α、TGF-β、PCIII 和 PCI 无变化；肺匀浆中 IL-10 水平升高（ = 0.007）；血液中性粒细胞中 MCP-1 表达减少（ = 0.009）；血液（ = 0.02）和 BALF（ = 0.008）中性粒细胞中 TNF-α表达减少；血液单核细胞中 IL-10 表达增加（ = 0.004）。结论：与对照大鼠相比，肥胖大鼠在接受内毒素刺激后，肺功能恶化程度较低，这与抗炎和抗纤维化作用以及血液和 BALF 中中性粒细胞和单核细胞/巨噬细胞表型的变化有关。
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