Development of experimental silicosis in inbred and outbred mice depends on instillation volume.
Development of experimental silicosis in inbred and outbred mice depends on instillation volume.
复制标题
近交系和远交系小鼠实验性硅肺病的发生取决于滴注量。
DOI：
10.1038/s41598-019-50725-9
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Pollard,KennethMichael
中科院分区：
文献类型：
--
作者：
Mayeux,JessicaM;Kono,DwightH;Pollard,KennethMichael
诱发实验性硅肺的方法有相当大的差异，剂量和暴露途径的影响已得到充分记录。然而，硅石悬浮液的体积在多大程度上改变了矽肺的分散度和严重程度还没有得到充分的研究。在本研究中，在近交系和远交系小鼠中确定了获得均匀分布和矽肺最大发病率和严重程度所需的结晶二氧化硅混悬液的最佳体积。二氧化硅分散，检测到的共同灵感与印度油墨和偏振光显微镜，是高度依赖于体积。此外，尽管在较低剂量和体积下检测到支气管周围炎、血管周围炎和支气管肺泡灌洗液细胞数量增加，但显著的肺泡炎需要暴露于50 μl中的5 mg二氧化硅。这种剂量和体积的经口滴注导致遗传异质多样性远交品系中更大的矽肺发病率以及更大的人类疾病中典型的矽肺肺泡炎症。这些发现强调了滴注量对实验性硅肺炎性病变的诱导、严重程度和类型的至关重要性。
There is considerable variation in methods to induce experimental silicosis with the effects of dose and route of exposure being well documented. However, to what extent the volume of silica suspension alters the dispersion and severity of silicosis has not been adequately investigated. In this study, the optimal volume of a crystalline silica suspension required to obtain uniform distribution and greatest incidence and severity of silicosis was determined in inbred and outbred mice. Silica dispersal, detected by co-inspiration with India ink and polarized light microscopy, was highly dependent upon volume. Furthermore, although peribronchitis, perivasculitis, and increases in bronchoalveolar lavage fluid cell numbers were detected a lower doses and volumes, significant alveolitis required exposure to 5 mg of silica in 50 μl. This dose and volume of transoral instillation led to a greater penetrance of silicosis in the genetically heterogeneous Diversity Outbred strain as well as greater alveolar inflammation typical of the silicosis in human disease. These findings underscore the critical importance of instillation volume on the induction, severity, and type of inflammatory pathology in experimental silicosis.