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樱花素可逆转慢性过敏性肺部炎症小鼠模型中的血管周围支气管和肺实质重塑。

Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation.

作者信息

Sakoda Camila Pivari Pedroso, de Toledo Alessandra Choqueta, Perini Adenir, Pinheiro Nathalia Montouro, Hiyane Meire Ioshie, Grecco Simone Dos Santos, de Fátima Lopes Calvo Tibério Iolanda, Câmara Niels Olsen Saraiva, de Arruda Martins Milton, Lago João Henrique Ghilardi, Righetti Renato Fraga, Prado Carla Máximo

机构信息

Department of Bioscience, Federal University of Sao Paulo, Santos, SP, Brazil.

Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.

出版信息

Acta Histochem. 2016 Jul;118(6):615-624. doi: 10.1016/j.acthis.2016.07.001. Epub 2016 Jul 15.

Abstract

BACKGROUND AND PURPOSE

Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma.

METHODS

Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30days and were treated with or without sakuranetin (20mg/kg/mice) or dexamethasone (5mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels.

RESULTS

We demonstrated that sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of sakuranetin was similar to the dexamethasone effect.

CONCLUSIONS AND IMPLICATIONS

Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.

摘要

背景与目的

哮喘是一种高患病率和高发病率的疾病,会产生高昂的住院和治疗费用。尽管气道参与了哮喘的病理生理过程,但也有证据表明血管和肺实质炎症及重塑的重要性,这可能导致哮喘患者出现肺部功能改变。我们的目的是评估使用从白花鬼针草(菊科)嫩枝中分离出的黄酮类化合物樱花素对实验性小鼠哮喘模型中血管和肺实质改变的治疗效果。

方法

雄性BALB/c小鼠用卵清蛋白进行30天的致敏方案,并接受或不接受樱花素(20mg/kg/小鼠)或地塞米松(5mg/kg/小鼠)治疗;然后,收集肺组织进行组织病理学分析。我们评估了肺血管和肺实质中的细胞外基质重塑(胶原纤维和弹性纤维)、炎症(嗜酸性粒细胞和核因子κB)以及氧化应激(8-异前列腺素)。对血管壁厚度以及血管内皮生长因子(VEGF)水平进行了量化。

结果

我们证明樱花素减少了肺血管和肺实质中嗜酸性粒细胞和弹性纤维的数量,这可能是由于肺中氧化应激、转录因子核因子κB和VEGF水平的降低。此外,它还降低了肺血管壁的厚度。该治疗对胶原纤维没有影响。在大多数参数中,樱花素的效果与地塞米松的效果相似。

结论与意义

樱花素具有抗炎和抗氧化作用,可预防该实验性哮喘模型中的血管和远端实质改变。

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