Wan Yu-Feng, Huang Zu-Hu, Jing Ke, Li Jun, Wang Yi, Xu Chuan-Qin, Chen Jian-Hui, Zheng Yu-Long
Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China. Department of Respiratory Diseases, Affiliated Huai'an Hospital of Xuzhou Medical College, Huaian 223002, People's Republic of China.
Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.
Respir Care. 2015 Jan;60(1):128-34. doi: 10.4187/respcare.03344. Epub 2014 Sep 23.
The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats.
Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed.
FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups.
Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.
炎症和免疫在慢性阻塞性肺疾病（COPD）治疗中的作用日益受到认可。COPD肺部抗炎/免疫调节与肺气肿之间的关系仍有待阐明。本研究旨在探讨阿奇霉素（Azm）对吸烟诱导的大鼠COPD中肺气肿发展的影响。
将50只Sprague-Dawley大鼠随机分为正常组、COPD组、生理盐水治疗组、Azm治疗组和左氧氟沙星治疗组（Lev）。通过酶联免疫吸附测定法测量血管内皮生长因子（VEGF）水平，通过支气管肺泡灌洗术测量中性粒细胞和巨噬细胞数量，通过蛋白质印迹法测量血管内皮生长因子（VEGF）和VEGF受体-2（VEGFR2）蛋白表达，以评估治疗效果。进行肺功能测量和组织病理学评估（平均线性截距和破坏指数）。
COPD组的第0.3秒用力呼气容积/用力肺活量（FEV0.3/FVC）和呼气峰值流速低于正常组。Azm治疗组的平均线性截距和破坏指数低于COPD组、生理盐水治疗组和Lev治疗组。Azm治疗组支气管肺泡灌洗液中的中性粒细胞和巨噬细胞数量低于COPD组、生理盐水治疗组和Lev治疗组。蛋白质印迹法证实，Azm治疗组肺匀浆中VEGF水平高于COPD组、生理盐水治疗组和Lev治疗组。Azm治疗组的VEGFR2蛋白表达高于COPD组、生理盐水治疗组和Lev治疗组。
Azm通过部分逆转吸烟诱导的大鼠COPD中炎症细胞（中性粒细胞和巨噬细胞）数量减少、VEGF分泌减少以及VEGFR2蛋白表达减少，减轻肺气肿。
