Early pulmonary disease manifestations in cystic fibrosis mice.
Early pulmonary disease manifestations in cystic fibrosis mice.
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DOI：
10.1016/j.jcf.2016.05.002
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Jacono FJ
中科院分区：
文献类型：
--
作者：
Darrah RJ;Mitchell AL;Campanaro CK;Barbato ES;Litman P;Sattar A;Hodges CA;Drumm ML;Jacono FJ
肺功能改变出现在囊性纤维化(CF)的早期，与记录的感染或肺部症状的出现无关。临床护理方面的新举措侧重于临床前疾病的检测和特征。因此，需要一种能够概括早期CF肺表型特征的动物模型。我们研究了年轻的CF小鼠，以确定它们是否表现出与早期CF肺表型一致的肺病理生理。用强迫振荡技术(FlexiVent)对12-16周龄同源基因C57BL/6 F508del和R117H CF小鼠的肺组织学和肺力学进行了观察。大气道阻力无明显差异。然而，在两种CF小鼠模型中，都发现了外周肺间室机械特性的显著差异，包括静态肺顺应性降低、弹性增加和组织阻尼增加。Cf组小鼠远端空域扩大，平均线形截距显著增加。携带两个独立的CFTR突变的年轻CF小鼠出现了外周肺间室伸展和扩张的能力受损，以及气体交换表面之间的距离增加。周围肺间室的这种改变的肺组织病理生理学改变，在没有感染的情况下发展，类似于CF患者的早期肺表型。
Altered pulmonary function is present early in the course of cystic fibrosis (CF), independent of documented infections or onset of pulmonary symptoms. New initiatives in clinical care are focusing on detection and characterization of pre-clinical disease. Thus, animal models are needed which recapitulate the pulmonary phenotype characteristic of early stage CF. We investigated young CF mice to determine if they exhibit pulmonary pathophysiology consistent with the early CF lung phenotype. Lung histology and pulmonary mechanics were examined in 12–16 week old congenic C57bl/6 F508del and R117H CF mice using a forced oscillation technique (flexiVent). There were no significant differences in the resistance of the large airways. However, in both CF mouse models, prominent differences in the mechanical properties of the peripheral lung compartment were identified including decreased static lung compliance, increased elastance and increased tissue damping. CF mice also had distal airspace enlargement with significantly increased mean linear intercept distances. An impaired ability to stretch and expand the peripheral lung compartment, as well as increased distances between gas exchange surfaces, were present in young CF mice carrying two independent Cftr mutations. This altered pulmonary histopathophysiology in the peripheral lung compartment, which develops in the absence of infection, is similar to the early lung phenotype of CF patients.
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影响因子：
10
作者：
Brennan, S;Hall, GL;Sly, PD
通讯作者：
Sly, PD
DOI：
10.1126/science.1255825
发表时间：
2014-08-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hoegger MJ;Fischer AJ;McMenimen JD;Ostedgaard LS;Tucker AJ;Awadalla MA;Moninger TO;Michalski AS;Hoffman EA;Zabner J;Stoltz DA;Welsh MJ
通讯作者：
Welsh MJ
影响因子：
3.6
作者：
Bonora, M;Bernaudin, JF;Brahimi-Horn, MC
通讯作者：
Brahimi-Horn, MC
影响因子：
24.3
作者：
Douglas, T. A.;Brennan, S.;Sly, P. D.
通讯作者：
Sly, P. D.
影响因子：
3.7
作者：
Hall GL;Logie KM;Parsons F;Schulzke SM;Nolan G;Murray C;Ranganathan S;Robinson P;Sly PD;Stick SM;AREST CF;Berry L;Garratt L;Massie J;Mott L;Poreddy S;Simpson S
通讯作者：
Simpson S