Schmid Otmar, Bolle Ines, Harder Volker, Karg Erwin, Takenaka Shinji, Schulz Holger, Ferron George A
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute for Inhalation Biology, 85758 Neuherberg/Munich, Germany.
J Aerosol Med Pulm Drug Deliv. 2008 Sep;21(3):291-307. doi: 10.1089/jamp.2008.0689.
Rats are used to test the toxicological and pharmacological effects of aerosol particles on the organism. For estimates of the delivered aerosol dose, lung deposition models provide a valuable tool. Here a previously developed deposition model for nonhygroscopic and hygroscopic aerosol particles in the lungs of man (Ferron et al., J. Aerosol Sci. 1988, 19:611) is adapted to the rat by implementing a lung structure for the rat combined with empirical equations for particle deposition due to impaction/sedimentation in the extrathoracic region and in bifurcations. To account for the effect of body weight (BW) on the physiological parameters (lung size, respiration frequency) we present BW-scaling laws with an estimated accuracy of about 16%. The present model shows good agreement with the measured total deposition (per breath) and other models from the literature to within the variability of the experimental data (20% absolute). Our calculations show that the variability of the experimental data is consistent with the combined effects from realistic variations in particle properties (mainly density) and physiological parameters (mainly activity level). For the alveolar region, which is of particular significance for pharmacological and health studies, we show that although the activity level may change the deposited dose by up to a factor of 2.2 for particles between 0.05 and 2.0 microm in diameter, the alveolar dose is almost independent (to within 10%) of activity level for particles between 0.5 and 1 microm, which makes this size range advantageous for pharmacological and toxicological experiments. The present model allows estimates of the total and regional particle dose deposited in the lungs of rats, which are consistent with experimental data. The advantage of the present model is that hygroscopic growth can be included in the calculations.
大鼠被用于测试气溶胶颗粒对生物体的毒理学和药理学作用。对于所输送气溶胶剂量的估算，肺部沉积模型提供了一个有价值的工具。在此，通过结合大鼠的肺部结构以及用于描述胸外区域和分叉处因撞击/沉降导致的颗粒沉积的经验方程，将先前开发的用于人体肺部非吸湿性和吸湿性气溶胶颗粒的沉积模型（Ferron等人，《气溶胶科学杂志》，1988年，19卷：611页）适配于大鼠。为了考虑体重（BW）对生理参数（肺大小、呼吸频率）的影响，我们提出了体重缩放定律，估计精度约为16%。当前模型与实测的总沉积量（每次呼吸）以及文献中的其他模型在实验数据的变异性范围内（绝对误差20%）显示出良好的一致性。我们的计算表明，实验数据的变异性与颗粒特性（主要是密度）和生理参数（主要是活动水平）的实际变化的综合影响一致。对于药理学和健康研究具有特别重要意义的肺泡区域，我们表明，尽管活动水平可能使直径在0.05至2.0微米之间的颗粒的沉积剂量变化高达2.2倍，但对于直径在0.5至1微米之间的颗粒，肺泡剂量几乎与活动水平无关（误差在10%以内），这使得该尺寸范围有利于进行药理学和毒理学实验。当前模型允许估算大鼠肺部沉积的总颗粒剂量和区域颗粒剂量，且与实验数据一致。当前模型的优点是可以在计算中纳入吸湿增长。
