Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling
Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling
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DOI：
10.1152/japplphysiol.00590.2004
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Suki, B
中科院分区：
文献类型：
--
作者：
Ito, S;Ingenito, EP;Suki, B
在肺气肿的发展过程中，呼吸气隙的扩张与结缔组织纤维网的破坏和重组有关。在这项研究中，通过直接滴注1.2 IU的猪胰弹性蛋白酶（PPE）建立了小鼠（C57 BL/6）肺气肿模型，并与用盐水处理的对照小鼠进行了比较。PPE治疗导致95%的肺泡扩大（P = 0.001），与准静态压力-容积曲线上29%的弹性降低沿着（P < 0.001）。在闭胸条件下，在几个呼气末正压下测量呼吸力学。PPE治疗组的动态组织弹性降低了19%（P < 0.001），抗弹性增加了9%（P < 0.05），谐波失真（胶原相关动态非线性的测量）增加了33%（P < 0.001）。在PPE治疗组中，代表总胶原含量的全肺羟脯氨酸含量高48%（P < 0.01），α-弹性蛋白含量低13%（P = 0.16）。气道阻力无显著差异（P = 0.7）。拉伸过程中分离的实质组织断裂的失效应力在PPE处理的小鼠中降低了40%（P = 0.002）。这些发现表明，在弹性蛋白溶解损伤后，异常胶原重塑可能在肺功能变化和机械力的各个方面发挥重要作用，导致进行性肺气肿。
Enlargement of the respiratory air spaces is associated with the breakdown and reorganization of the connective tissue fiber network during the development of pulmonary emphysema. In this study, a mouse (C57BL/6) model of emphysema was developed by direct instillation of 1.2 IU of porcine pancreatic elastase (PPE) and compared with control mice treated with saline. The PPE treatment caused 95% alveolar enlargement (P = 0.001) associated with a 29% lower elastance along the quasi-static pressure-volume curves (P < 0.001). Respiratory mechanics were measured at several positive end-expiratory pressures in the closed-chest condition. The dynamic tissue elastance was 19% lower (P < 0.001), hysteresivity was 9% higher (P < 0.05), and harmonic distortion, a measure of collagen-related dynamic nonlinearity, was 33% higher in the PPE-treated group (P < 0.001). Whole lung hydroxyproline content, which represents the total collagen content, was 48% higher (P < 0.01), and alpha-elastin content was 13% lower (P = 0.16) in the PPE-treated group. There was no significant difference in airway resistance (P = 0.7). The failure stress at which isolated parenchymal tissues break during stretching was 40% lower in the PPE-treated mice (P = 0.002). These findings suggest that, after elastolytic injury, abnormal collagen remodeling may play a significant role in all aspects of lung functional changes and mechanical forces, leading to progressive emphysema.