Alterations in lung mechanics in decorin-deficient mice
Alterations in lung mechanics in decorin-deficient mice
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DOI：
10.1152/ajplung.00089.2004
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发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Ludwig, MS
中科院分区：
文献类型：
--
作者：
Fust, A;LeBellego, F;Ludwig, MS
核心蛋白聚糖是一种小的富含亮氨酸的蛋白聚糖，具有广泛的组织分布，是大多数组织中胶原蛋白正常原纤维形成所必需的。因为胶原蛋白在决定肺的弹性行为中是重要的，我们假设肺组织力学将在突变小鼠中改变，其中单个核心蛋白聚糖基因被靶向缺失（Dcn-/-）废除。在C57 B1/6小鼠（Dcn-/-和Dcn+/+）中使用向气管递送具有多个频率的体积信号的小动物呼吸机测量呼吸系统的复阻抗。一个恒定的相位模型拟合计算气道阻力（R-aw），组织阻尼，和组织弹性。呼吸系统顺应性（C-rs）在逐步放气过程中从压力容积曲线测量。切除肺，并将实质组织条固定在器官浴中，用于组织阻抗和准静态长度-应力曲线的体外测量。此外，通过免疫组织化学和免疫印迹法检查肺组织。在体内，在Dcn-/-小鼠中，R-aw降低，Crs增加。类似地，在体外，长度-应力曲线显示Dcn-/-小鼠中条带的顺应性增加。Dcn-/-小鼠肺组织机械行为的这些改变支持核心蛋白聚糖在肺胶原网络形成中的关键作用。
Decorin, a small leucine-rich proteoglycan with a widespread tissue distribution, is required for the normal fibrillogenesis of collagen in most tissues. Because collagen is important in determining the elastic behavior of the lung, we hypothesized that lung tissue mechanics would be altered in a mutant mouse in which the single decorin gene was abrogated by targeted deletion (Dcn-/-). Complex impedance of the respiratory system was measured in C57Bl/6 mice (Dcn-/- and Dcn+/+) using a small animal ventilator that delivers a volume signal with multiple frequencies to the trachea. A constant-phase model was fit to calculate airway resistance (R-aw), tissue damping, and tissue elastance. Compliance of the respiratory system (C-rs) was measured from a pressure volume curve during stepwise deflations. Lungs were excised, and parenchymal tissue strips were mounted in an organ bath for in vitro measurement of tissue impedance and quasistatic length-stress curves. In addition, pulmonary tissue was examined by immunohistochemistry and immunoblotting. In vivo, in the Dcn-/- mice, R-aw was decreased and Crs was increased. Similarly, in vitro, length-stress curves showed increased compliance of the strips in the Dcn-/- mice. These alterations in lung tissue mechanical behavior in Dcn-/- mice support a critical role for decorin in the formation of the lung collagen network.