CORRELATION BETWEEN PARTICLE-SIZE, IN-VIVO PARTICLE PERSISTENCE, AND LUNG INJURY
CORRELATION BETWEEN PARTICLE-SIZE, IN-VIVO PARTICLE PERSISTENCE, AND LUNG INJURY
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DOI：
10.2307/3432080
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发表时间：
1994-10-01
影响因子：
10.4
通讯作者：
LEHNERT, BE
中科院分区：
文献类型：
--
作者：
OBERDORSTER, G;FERIN, J;LEHNERT, BE
剂量学参数，如吸入颗粒在不同肺室中的沉积、清除、滞留、易位和溶解，可能对颗粒在肺中的持久性很重要，并可能与不良肺效应相关。我们使用一个模型来研究这种相关性，该模型涉及具有相同晶体结构（锐钛矿）的两种粒径（直径20 nm，超细；直径250 nm，细）的TiO2颗粒。对大鼠进行了为期12周的吸入实验，结果显示这两种颗粒在下呼吸道有类似的团块沉积。与大颗粒相比，超细颗粒在动物肺部引发了持续的高炎症反应。在暴露后（长达1年），细粒和超细粒TiO2在肺泡空间本身的滞留没有区别。然而，注意到颗粒类型之间的以下差异：在数量上（超细TiO2的滞留时间明显延长）和质量上（超细TiO2向肺间质移位和在肺间质滞留的增加），总肺滞留量有显著差异；更大的上皮效应（II型细胞增殖，Kohn孔闭塞）和超细TiO2间质纤维化灶的开始；通过测试颗粒的清除来测量超细TiO2暴露后肺泡巨噬细胞功能的显著持续损伤。观察到颗粒表面积与效应之间的相关性。通过对暴露后不同肺室中TiO2的不良反应与剂量学参数的比较发现，TiO2在肺泡和肺间质中作用的持久性与颗粒在各自肺室中的持久性有关。
Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.