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模拟颗粒在Balb/c小鼠呼吸道中的沉积。

Modeling particle deposition in the Balb/c mouse respiratory tract.

作者信息

Winkler-Heil Renate, Hofmann Werner

机构信息

a Division of Physics and Biophysics , Department of Chemistry and Physics of Materials, University of Salzburg , Salzburg , Austria.

出版信息

Inhal Toxicol. 2016;28(4):180-91. doi: 10.3109/08958378.2016.1148801.

Abstract

The mouse lung has become increasingly important as a surrogate of the human lung for inhalation risk assessment. The main structural difference between the two lungs is that the airway branching of the human lung is relatively symmetric, while that of the mouse lung is distinctly asymmetric or monopodial. The objectives of this study were to develop a stochastic, asymmetric particle deposition model for the Balb/c mouse and to compare predicted deposition patterns with those in the human lung. The asymmetric bronchial airway geometry of the Balb/c mouse was based on a statistical analysis of several lung casts, while, in the absence of pertinent data, the asymmetric acinar airway geometry was represented by an allometrically scaled-down version of the rat acinar region, assuming structural similarity. Deposition of inhaled particles in nasal, bronchial and acinar airways for mouse-specific breathing conditions was computed with the Monte Carlo deposition model IDEAL-mouse. While total deposition for submicron particles decreases with increasing diameter in a fashion similar to that in the human lung, the effect of inhalability and nasal pre-filtration significantly reduces total deposition in the mouse lung for particles with diameters greater than about 3 μm. The most notable difference between submicron particle deposition in the mouse and human airways is the shift of the deposition distribution from distal airway generations in the human lung to upper airway generations in the mouse lung. However, if plotted as a function of airway diameter, both deposition distributions are quite similar, indicating that airway diameter may be a more appropriate morphometric parameter for extrapolation purposes than airway generation.

摘要

作为人类肺部吸入风险评估的替代物,小鼠肺部的重要性日益凸显。这两种肺部的主要结构差异在于,人类肺部的气道分支相对对称,而小鼠肺部的气道分支则明显不对称或呈单足状。本研究的目的是为Balb/c小鼠开发一种随机、不对称的颗粒沉积模型,并将预测的沉积模式与人类肺部的沉积模式进行比较。Balb/c小鼠不对称的支气管气道几何形状基于对多个肺铸型的统计分析,而在缺乏相关数据的情况下,假设结构相似,不对称的腺泡气道几何形状由大鼠腺泡区域按比例缩小的版本表示。使用蒙特卡洛沉积模型IDEAL-mouse计算了在小鼠特定呼吸条件下,吸入颗粒在鼻腔、支气管和腺泡气道中的沉积情况。虽然亚微米颗粒的总沉积量随直径增加而降低,其方式与人类肺部相似,但对于直径大于约3μm的颗粒,可吸入性和鼻腔预过滤的影响显著降低了小鼠肺部的总沉积量。小鼠和人类气道中亚微米颗粒沉积的最显著差异在于,沉积分布从人类肺部的远端气道代转移到了小鼠肺部的上呼吸道代。然而,如果将其绘制为气道直径的函数,两种沉积分布相当相似,这表明对于外推目的而言,气道直径可能是比气道代更合适的形态计量参数。

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