Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats
Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats
复制标题
口服 N-乙酰半胱氨酸可减轻吸烟引起的慢性阻塞性肺病大鼠的肺气肿和肺泡间隔细胞凋亡
DOI：
10.1111/j.1440-1843.2009.01511.x
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发表时间：
2009-04-01
期刊：
影响因子：
6.9
通讯作者：
Wu, Jie
中科院分区：
文献类型：
--
作者：
Cai, Shan;Chen, Ping;Wu, Jie
细胞凋亡在肺气肿/COPD肺破坏中的作用正日益被认识到。抗氧化剂与COPD肺中肺泡间隔细胞凋亡的关系仍有待阐明。为探讨抗氧化剂N-乙酰半胱氨酸（N-acetylcysteine，NAC）对吸烟诱导的慢性阻塞性肺疾病（COPD）大鼠肺气肿形成和肺泡间隔细胞凋亡的影响，将SD大鼠随机分为正常组、COPD组、假手术组和NAC组。通过ELISA法检测支气管肺泡灌洗液中血管内皮生长因子（VEGF）水平，Western blotting法检测VEGF和VEGF受体2（VEGFR 2）蛋白表达，TUNEL法检测肺泡隔细胞凋亡指数（AI）。结果COPD组FEV 0. 3/FVC、PEF均低于正常组，肺功能指标均低于正常组。NAC治疗组的MLI和DI低于COPD或假治疗组。免疫印迹法证实，NAC治疗组BAL液中VEGF水平高于COPD组。NAC治疗组VEGFR 2蛋白表达高于COPD组。NAC治疗组的AI显著低于COPD组。肺泡隔细胞凋亡指数与肺泡灌洗液中VEGF水平呈负相关，NAC可部分逆转吸烟诱导的COPD大鼠肺组织VEGF分泌和VEGFR 2蛋白表达的下降，减轻肺损伤、肺气肿和肺泡隔细胞凋亡。
The role of apoptosis in lung destruction in emphysema/COPD is increasingly being recognized. The relationship between anti-oxidants and alveolar septal cell apoptosis in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of the anti-oxidant, N-acetylcysteine (NAC), on the development of emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats.Sprague-Dawley rats (n = 48) were randomly assigned to normal, COPD, sham and NAC groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) in BAL fluid by ELISA, VEGF and VEGF receptor-2 (VEGFR2) protein expression by western blotting, and the apoptotic index (AI) of alveolar septal cells by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Histopathological evaluations (mean linear intercept (MLI), destructive index (DI)) and lung function measurements were performed.FEV0.3/FVC and PEF were lower in the COPD group than in the normal group. MLI and DI were lower in the NAC-treated group than in the COPD or sham-treated groups. As confirmed by western blotting, the levels of VEGF in BAL fluid were higher in the NAC-treated group than in the COPD group. VEGFR2 protein expression was higher in the NAC-treated group than in the COPD group. The AI was significantly lower in the NAC-treated group than in the COPD group. There was an inverse correlation between levels of VEGF in BAL fluid and the AI of alveolar septal cells.NAC attenuates lung damage, pulmonary emphysema and alveolar septal cell apoptosis by partly reversing the decrease in VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.