PULMONARY RETENTION OF ULTRAFINE AND FINE PARTICLES IN RATS
PULMONARY RETENTION OF ULTRAFINE AND FINE PARTICLES IN RATS
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DOI：
10.1165/ajrcmb/6.5.535
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发表时间：
1992-05-01
影响因子：
6.4
通讯作者：
PENNEY, DP
中科院分区：
文献类型：
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作者：
FERIN, J;OBERDORSTER, G;PENNEY, DP
在气溶胶研究中，主要考虑颗粒尺寸在呼吸道颗粒沉积中所起的作用。本研究探讨了初级颗粒尺寸可能影响颗粒沉积后的命运的可能性。大鼠暴露于雾化超细（直径约 21 nm）或细（直径约 250 nm）二氧化钛 (TiO2) 颗粒 12 周。其他大鼠通过气管内滴注暴露于不同尺寸（12、21、230 和 250 nm）的 TiO2 颗粒。对大鼠肺进行广泛灌洗后，对灌洗肺、灌洗液和淋巴结中的颗粒含量进行分析。还使用未灌洗的肺进行电子和光学显微镜检查。急性滴注和亚慢性吸入研究均表明，同等质量的超细颗粒（约 20 nm）比细颗粒（约 250 nm）更能进入肺间质。颗粒数量的增加和颗粒尺寸的减小促进了颗粒进入间质。颗粒进入间质的易位似乎是颗粒数量的函数，并且该过程似乎与颗粒尺寸、递送剂量和递送剂量率有关。较小颗粒优先易位至间质的净效应是延长其肺滞留时间。吸入暴露 12 周后，超细颗粒的肺部清除速度（t1/2 = 501 天）比较大颗粒（t1/2 = 174 天）慢。肺泡内未被肺泡巨噬细胞吞噬的颗粒被肺泡I型上皮细胞摄取，这可能是颗粒进入间质的第一步。肺泡清除高度不溶性颗粒的两种不同途径——通过气道和通过间质淋巴途径——似乎通过大鼠的支气管相关淋巴组织相互连接。 TiO2 颗粒易位到间质中伴随着急性炎症反应，如灌洗细胞中多形核白细胞 (PMN) 增加所表明的那样。在暴露后的时期，虽然肺负荷仍然大幅升高，但灌洗后的 PMN 数量几乎降至对照值。这表明炎症受到暴露期间发生的过程的影响，而较少受到肺负荷或暴露后颗粒重新分布的影响。
In aerosol research, particle size has been mainly considered in the context of the role it plays in particle deposition along the respiratory tract. The possibility that the primary particle size may affect the fate of particles after they are deposited was explored in this study. Rats were exposed for 12 wk to aerosolized ultrafine (approximately 21 nm diameter) or fine (approximately 250 nm diameter) titanium dioxide (TiO2) particles. Other rats were exposed to TiO2 particles of various sizes (12, 21, 230, and 250 nm) by intratracheal instillation. After the rat lungs were extensively lavaged, analysis of particle content in the lavaged lungs, lavage fluid, and of lymphatic nodes was performed. Electron and light microscopy was also performed using unlavaged lungs. Both acute instillation and subchronic inhalation studies showed that ultrafine particles (approximately 20 nm) at equivalent masses access the pulmonary interstitium to a larger extent than fine particles (approximately 250 nm). An increasing dose in terms of particle numbers and a decreasing particle size promoted particle access into the interstitium. The translocation of particles into the interstitium appeared to be a function of the number of particles, and the process appeared to be related to the particle size, the delivered dose, and the delivered dose rate. A net effect of the preferential translocation of the smaller particles into the interstitium was a prolongation in their lung retention. After the 12-wk inhalation exposure, pulmonary clearance of ultrafine particles was slower (t1/2 = 501 days) than of larger particles (t1/2 = 174 days). Particles not phagocytized by alveolar macrophages in the alveoli were taken up by alveolar type I epithelial cells, which was probably the first step for interstitial access of particles. The two distinct pathways for alveolar clearance of highly insoluble particles-via the airways and via the interstitial-lymphatic route-seem to be interconnected by bronchus-associated lymphoid tissue in rats. TiO2 particle translocation into the interstitium was accompanied by an acute inflammatory response, as indicated by polymorphonuclear leukocyte (PMN) increases among lavaged cells. In the postexposure period, although the lung burdens were still substantially elevated, the lavaged PMN numbers decreased to almost control values. This suggests that inflammation was affected by the processes occurring during exposure and less by the lung burden or by particle redistribution after exposure.