Elevated oxidative stress and reciprocal reduction of vascular endothelial growth factor levels with severity of COPD
Elevated oxidative stress and reciprocal reduction of vascular endothelial growth factor levels with severity of COPD
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DOI：
10.1378/chest.128.5.3191
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发表时间：
2005-11-01
期刊：
影响因子：
9.6
通讯作者：
Yoshikawa, J
中科院分区：
文献类型：
--
作者：
Kanazawa, H;Yoshikawa, J
研究目的：关于COPD发病机制的流行理论认为是氧化剂和抗氧化剂之间的失衡。然而，据报道，血管内皮生长因子(VEGF)的减少可能影响COPD的发病机制。因此，这项研究旨在检验氧化应激和血管内皮生长因子水平以及COPD严重程度之间的差异。设计：对照横断面分析。地点：大学医院。参与者：12名健康对照组和57名COPD患者。根据全球慢性阻塞性肺疾病倡议的分类，这些COPD患者被分为四组(轻度COPD 14例；中度COPD 15例；重度COPD 16例；极重度COPD 12例)。测量和结果：检测所有受试者的痰标本中的炎症标志物、氧化应激程度和血管内皮生长因子水平。COPD患者诱导痰中的氮氧化物水平显著高于健康对照组，且随着COPD严重程度的增加而增加。相反，过氧亚硝酸盐抑制活性随着COPD严重程度的增加而降低。因此，平均(SD)过亚硝酸盐应激(即氮氧化物水平/过亚硝酸盐抑制活性比率)。与健康对照组相比，随着COPD严重程度的增加(轻度COPD：8.40；SD1.5；p=0.02；中度COPD：10.8；SD，1.4；p<；0.0001；重度COPD：14.5；SD，2.5；p<；0.0001；极重度COPD：18.3；SD，4.1；p<；0.0001)急剧增加。诱导痰中血管内皮生长因子水平随着慢性阻塞性肺疾病的严重程度而递减(轻度慢性阻塞性肺病：1,360pg/m L；SD，800pg/m l；p=0.97；中度：1,180pg/m l；SD，760pg/m l；p=0.5；重度：650pg/m l；SD，450pg/m l；p=0.007；极重度COPD：480pg/m l，SD，240pg/m l；p=0.002)。此外，COPD患者的过氧亚硝酸盐抑制活性较健康对照组的平均水平加速下降。结论：随着COPD病情的加重，诱导痰中氧化应激水平的升高和诱导痰中的VEGF水平的降低是显著的。因此，氧化应激介导的上皮细胞损伤可能导致肺组织中血管内皮生长因子水平降低，从而促进COPD的发生发展。
Study objectives: The prevalent theory concerning the pathogenesis of COPD is that it is an imbalance between oxidants and antioxidants. However, it has been reported that a decrease in vascular endothelial growth factor (VEGF) might affect the pathogenesis of COPD. Therefore, this study was designed to examine the differences between oxidative stress and VEGF levels, and the severity of COPD.Design: Controlled cross-sectional analysis.Setting: University hospital.Participants: Twelve healthy control subjects and 57 COPD patients were included in this study. These COPD patients were divided into four groups based on the Global Initiative for Chronic Obstructive Lung Disease classification (mild COPD, 14 patients; moderate COPD, 15 patients; severe COPD, 16 patients; very severe COPD, 12 patients).Measurements and results: Inflammatory markers, degree of oxidative stress, and VEGF levels were examined in sputum samples from all subjects. Nitrogen oxide levels in induced sputum were significantly higher in COPD patients than in healthy control subjects, and they increased with increases in the severity of COPD. In contrast, peroxynitrite inhibitory activity decreased with increases in the severity of COPD. Therefore, the mean (SD) peroxynitrite stress (ie, the nitrogen oxide level/peroxynitrite inhibitory activity ratio). steeply increased with increases in the severity of COPD (mild COPD: 8.4; SD, 1.5; p = 0.02; moderate COPD: 10.8; SD, 1.4; p < 0.0001; severe COPD: 14.5; SD, 2.5; p < 0.0001; very severe COPD: 18.3; SD, 4.1; p < 0.0001) compared with that of healthy control subjects. VEGF levels in induced sputum reciprocally decreased with severity of COPD (mild COPD: 1,360 pg/mL; SD, 800 pg/mL; p = 0.97; moderate COPD: 1,180 pg/mL; SD, 760 pg/mL; p = 0.50; severe COPD: 650 pg/mL; SD, 450 pg/mL; p = 0.007; very severe COPD: 480 pg/mL, SD, 240 pg/mL; p = 0.002). In addition, peroxynitrite inhibitory, activity in COPD patients exhibited an accelerated decline from the mean VEGF level in healthy control subjects.Conclusions: Elevated oxidative stress levels and a reciprocal reduction of VEGF levels in induced sputum were prominent with increases in the severity of COPD. Thus, epithelial cell injury mediated by oxidative stress may induce the decrease in lung VEGF levels, resulting in the promotion of the development of COPD.