Methodology for the measurement of mucociliary function in the mouse by scintigraphy
Methodology for the measurement of mucociliary function in the mouse by scintigraphy
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DOI：
10.1152/jappl.2001.90.3.1111
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发表时间：
2001-03-01
影响因子：
3.3
通讯作者：
Miller, LM
中科院分区：
文献类型：
--
作者：
Foster, WM;Walters, DM;Miller, LM
这项研究的目的是建立一种测量小型实验啮齿动物(如小鼠)呼吸道粘液纤毛清除的闪烁照相方法。以前的研究已经确定了小鼠呼吸道中存在的分泌细胞类型，但对粘液运输系统的分析一直局限于组织外植体的体外检查或单个呼吸道--气管的体内侵入性测量。三种方法用来沉积不溶的放射性同位素胶体颗粒：口咽吸入、气管内滴注和仅经鼻吸入。用伽马相机显示颗粒在下呼吸道的初始分布，并间歇性地跟踪颗粒的清除超过6h，最后是分娩后24h。为了寻找组织炎症的证据，对不同亚组的小鼠进行了灌洗，并对其他小鼠进行了重新研究，以确定方法的重复性。吸入和滴注给药方法导致沉积的放射性在肺内的分布更大，即类似于总呼吸道放射性的60%-80%，而仅经鼻的气雾剂技术在肺内的分布达到32%。然而，气雾剂技术最大限度地增加了在24小时内清除呼吸道的颗粒的比例，即沉积在呼吸道上皮表面并通过粘液纤毛功能清除的颗粒，因此24小时时通过雾化吸入传递的肺滞留平均为57%，而吸入或气管内滴注技术的肺滞留大于或等于80%。以炎症细胞和趋化细胞因子为标准，颗粒给药方法不会引起肺部炎症/损伤。核素扫描可以识别小鼠下呼吸道的颗粒沉积和清除，是非侵入性的，可重复性，并包括重新研究和肺灌洗的能力，当考虑到时间进程或慢性治疗时。
The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by gamma -camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., similar to 60-80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and greater than or equal to 80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.