Ventilatory responses to hypercapnia and hypoxia in conscious cystic fibrosis knockout mice Cftr-/-
Ventilatory responses to hypercapnia and hypoxia in conscious cystic fibrosis knockout mice Cftr-/-
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DOI：
10.1203/01.pdr.0000117841.81730.2b
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Brahimi-Horn, MC
中科院分区：
文献类型：
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作者：
Bonora, M;Bernaudin, JF;Brahimi-Horn, MC
本研究旨在检查囊性纤维化基因敲除小鼠（Cftr（-/-））与杂合（Cftr（+/-））或野生型（Cftr（+/+））同窝小鼠相比的净化性能和肺组织病理学。使用全身体积描记法记录清醒动物的通气。在空气呼吸期间以及对不同水平的高碳酸血症（2、4、6或8%CO2）或缺氧（14、12、10或8%O-2）的反应中，测量潮气量（V-T）、呼吸频率（f）和每分钟通气量（V-E）。Cftr（+/-）和Cftr（+/+）的结果合并到一个对照组中，因为它们没有差异。在空气中和对高碳酸血症的反应中，Cftr（-/-）小鼠和对照组的V-E、V-T和f相似。在分级缺氧期间，由于较低的f，Cftr（-/-）小鼠在10和8%0时V1降低。组织学显示Cftr（-/-）小鼠既没有炎症也没有气道阻塞。形态学分析显示肺泡扩张是由于扩张或发育受损。总之，囊性纤维化基因敲除小鼠对高碳酸血症有正常的基线呼吸和呼吸反应，但对严重缺氧的呼吸反应降低。与形态测定分析相关的后一结果表明，Cftr（-/-）小鼠可能表现出呼吸系统的不成熟。
This study was designed to examine the ventilatory performance and the lung histopathology of cystic fibrosis knockout mice (Cftr(-/-)) compared with heterozygous (Cftr(+/-)) or wildtype (Cftr(+/+)) littermates. Ventilation was recorded in conscious animals using whole-body plethysmography. Tidal Volume (V-T), respiratory frequency (f), and minute ventilation (V-E) were measured during air breathing and in response to various levels of hypercapnia (2, 4, 6, or 8% CO2) or hypoxia (14, 12, 10, or 8% O-2). The results for Cftr(+/-) and Cftr(+/+) were pooled into one control group because they did not differ. In air and in response to hypercapnia, V-E, V-T, and f were similar in Cftr(-/-) mice and in controls. During graded hypoxia, V, was decreased in Cftr(-/-) mice at 10 and 8% 0, because of a lower f. Histology showed neither inflammation nor obstruction of airways in Cftr(-/-) mice. Morphometric analysis showed alveolar dilation as a result of either distension or impaired development. In conclusion, cystic fibrosis knockout mice have normal baseline breathing and ventilatory response to hypercapnia but a decreased ventilatory response to severe hypoxia. This latter result associated with the morphometric analysis suggests that Cftr(-/-) mice may exhibit immaturity of the respiratory system.