Resolution of acute lung injury and inflammation: a translational mouse model.
Resolution of acute lung injury and inflammation: a translational mouse model.
复制标题
DOI：
10.1183/09031936.00093911
复制
发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Takata M
中科院分区：
文献类型：
--
作者：
Patel BV;Wilson MR;Takata M
以前的急性肺损伤(ALI)动物模型是有限的，因为它们只复制了临床ALI复杂病理生物学的一部分。在这里，我们建立了一种翻译的ALI小鼠模型，该模型不仅反映了ALI的主要临床和病理特征，而且能够研究ALI的解决方案。麻醉小鼠经口气管内滴注盐酸。在注射后的即刻阶段，小鼠被小心地补充氧气以避免死亡。在特定的时间点，通过血气、呼吸力学、支气管肺泡灌洗液分析、肺泡液清除和肺组织学来评估肺损伤。动物表现出显著的体重减轻、氧合降低、呼吸弹性增加和肺部炎症(肺泡内白细胞内流/细胞因子水平和组织损伤评分)。此外，小鼠表现出肺泡-毛细血管屏障功能障碍/上皮损伤，表现为肺泡蛋白、肺湿/干重比和晚期糖基化终产物可溶性受体增加，以及肺泡液清除减少。这些损伤参数在第1-3天达到峰值，随后在第5-10天几乎完全恢复。结果表明，酸吸入消解模型是研究ALI损伤、炎症、纤维化、消解和修复过程的有力实验工具。
Previous animal models of acute lung injury (ALI) are limited as they only reproduce part of the complex pathobiology of clinical ALI. Here we develop a translational mouse model of ALI, which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution. Anaesthetised mice underwent orotracheal instillation of hydrochloric acid. During the immediate period after instillation, mice were carefully maintained with supplemental oxygen to avoid mortality. At specified time points, lung injury was assessed by blood gases, respiratory mechanics, analysis of bronchoalveolar lavage fluid, alveolar fluid clearance and lung histology. Animals exhibited significant weight loss, decreased oxygenation, increased respiratory elastance, and pulmonary inflammation (intra-alveolar leucocyte influx/ cytokine levels and histological injury scores). Moreover, mice displayed alveolar-capillary barrier dysfunction/epithelial injury as reflected by increased alveolar protein, lung wet/dry weight ratio and soluble Receptor for Advanced Glycation End-products, as well as reduced alveolar fluid clearance. These injury parameters peaked between days 1-3, followed by almost complete recovery over days 5-10. Histology showed evidence of fibrosis at day 10. The results indicate that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALI.
登录
查看更多内容
影响因子：
9.6
作者：
Briot R;Frank JA;Uchida T;Lee JW;Calfee CS;Matthay MA
通讯作者：
Matthay MA
影响因子：
4.3
作者：
Bastarache, Julie A.;Blackwell, Timothy S.
通讯作者：
Blackwell, Timothy S.
DOI：
10.1164/ajrccm/142.6_pt_1.1250
发表时间：
1990-12-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
MATTHAY, MA;WIENERKRONISH, JP
通讯作者：
WIENERKRONISH, JP
影响因子：
5.7
作者：
Henzler, Dietrich;Hochhausen, Nadine;Zhang, Haibo
通讯作者：
Zhang, Haibo
影响因子：
4.4
作者：
Fukunaga, K;Kohli, P;Levy, BD
通讯作者：
Levy, BD