Morphological mechanism of the development of pulmonary emphysema in klotho mice
Morphological mechanism of the development of pulmonary emphysema in klotho mice
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DOI：
10.1073/pnas.0607882104
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发表时间：
2007-02-13
影响因子：
11.1
通讯作者：
Mishima, Michiaki
中科院分区：
文献类型：
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作者：
Sato, Atsuyasu;Hirai, Toyohiro;Mishima, Michiaki
分形几何的概念对于分析自然界中常见的不规则和复杂结构是有用的。本研究运用这一概念探讨了klotho小鼠在乳喂养后表现出类似衰老的特征并发生肺气肿的结构机制。我们计算了周长和表征形状的尺寸之间的关系，以及从组织学幻灯片中确定的终端空气空间的累积频率和大小之间的关系，发现两者的关系都遵循具有分形性质的幂律。然而，与形状和大小相关的分形维数（Dsn）在klotho小鼠中显著低于对照组。此外，在klotho小鼠中，Dsn随着年龄的增长而下降，但平均线性截距没有显著变化。当klotho小鼠被喂食缺乏维生素d的食物时，这些异常的形态变化恢复了。先前描述的形态学模型模拟表明，随机破坏，即破坏过程均匀地发生在肺部，比通常在吸烟相关的人类肺气肿中看到的相关破坏更符合数据。这些结果表明，klotho小鼠肺部的病理变化不是由局部原因引起的，而是由与维生素d异常激活有关的全身性原因引起的。klotho小鼠肺气肿的形态发生和使用分形几何的形态学分析可能有助于理解人类肺气肿实质破坏的进行性性质和原因。
The concept of fractal geometry is useful for the analysis of irregular and complex structures often seen in nature. Here we apply this concept to investigate the structural mechanism of the development of pulmonary emphysema in the klotho mouse, which, after milk feeding, exhibits characteristics resembling aging and develops emphysema. We calculated the relationships between perimeter and size characterizing shape and between cumulative frequency and size of the terminal air spaces identified from histologic slides and found that both relations followed a power law with fractal properties. However, the fractal dimensions related to the shape and size (Dsn) in the klotho mice were significantly lower than in controls. Additionally, in the klotho mice, Dsn decreased with age without significant change in mean linear intercept. These abnormal morphological changes were restored when the klotho mice were fed with a vitamin D-deficient diet. Previously undescribed morphological model simulations showed that a random destruction, in which the destruction process occurs homogeneously in the lungs, was more consistent with the data than a correlated destruction that is usually seen in smoking-related human emphysema. These results suggest that the pathological changes in the lungs of the klotho mice are derived not from localized causes, but from systemic causes that are related to abnormal activation of vitamin D. The morphogenesis of emphysema in the klotho mice and morphological analyses using fractal geometry may contribute to the understanding of the progressive nature and cause of parenchymal destruction in human emphysema.