Department of Pharmacology, Kobe Pharmaceutical University, Motoyamakita, Higashinada, Japan.
Biol Pharm Bull. 2009 Sep;32(9):1559-64. doi: 10.1248/bpb.32.1559.
Exposure of animals to cigarette smoke for longer than 3 months leads to the development of chronic obstructive pulmonary disease (COPD) showing pulmonary emphysema. We attempted to create a COPD model with emphysema that could be established in a shorter period of time. Guinea pigs were intratracheally treated once a day on days 0-3, 5-8, 10-13 and 15-18 with a cigarette smoke solution (CSS), which was prepared by bubbling a stream of smoke into saline. Additionally, lipopolysaccharide (LPS) was administered intratracheally as an exacerbation factor on days 4, 9 and 14. By day 19, there was a gradual elevation of specific airway resistance (sRaw). In addition, both residual volume and functional residual capacity were found to be significantly higher on day 19. In the lungs, there was a marked increase in leukocytes, especially neutrophils. Histologically, we observed epithelial hyperplasia and emphysema. On the other hand, daily oral administration of theophylline during the administration of CSS and LPS suppressed the sRaw increase and the epithelial hyperplasia, but not other functional structural changes. In conclusion, we established an experimental COPD model in guinea pigs by using intratracheal instillations of CSS and LPS over a considerably shorter term than has been reported for other models.
动物暴露于香烟烟雾中超过 3 个月可导致慢性阻塞性肺疾病（COPD）的发展，表现为肺气肿。我们试图创建一种肺气肿的 COPD 模型，使其能够在更短的时间内建立。豚鼠在第 0-3、5-8、10-13 和 15-18 天每天经气管内给予香烟烟雾溶液（CSS）一次，该溶液通过将烟雾吹入盐水中制备。此外，在第 4、9 和 14 天经气管内给予脂多糖（LPS）作为加重因素。到第 19 天，特异性气道阻力（sRaw）逐渐升高。此外，第 19 天的残气量和功能残气量也明显升高。在肺部，白细胞尤其是中性粒细胞明显增加。组织学上，我们观察到上皮细胞增生和肺气肿。另一方面，在 CSS 和 LPS 给药期间每天口服茶碱可抑制 sRaw 增加和上皮细胞增生，但不能抑制其他功能结构改变。总之，我们通过在豚鼠中经气管内滴注 CSS 和 LPS 建立了一种实验性 COPD 模型，其建立时间明显短于其他模型报道的时间。
