The effect of age on crystalline silica-induced pulmonary toxicity-aged rats

The effect, if any, of age on the pulmonary toxicity induced by Min-U-Sil 5 crystalline silica exposure was investigated in rats. As part of the study, the changes in global gene expression profiles in the blood and lungs of the animals were determined. To conduct these studies, to determine if age influences the pulmonary response to crystalline silica exposure, two different age groups of healthy, male F344 rats were used. In this study the old age group of rats (12 months old at the time of exposure) was exposed to either air or crystalline silica (Min-U-Sil 5) (15 mg/m3, 6 hours/day, 5 days) by whole body inhalation. The old age group of rats simulates a group of workers who would be 45 to 50 years old. At two crystalline silica post-exposure time periods (1-day and 6-months) animals were euthanized and pulmonary inflammatory, cytotoxic, and oxidant responses were determined. Analysis of bronchoalveolar lavage parameters of toxicity such as oxidant generation and inflammation revealed significant changes in pulmonary toxicity in the crystalline silica exposed rats compared with the time-matched, air exposed control rats. The blood gene expression profiles showed only minimal changes, at both the time points, in the crystalline silica exposed rats compared with the controls. Specifically, no genes were significantly differentially expressed (fold change >1.5 and FDR p<0.05) in the one-day post-exposure group and only 6 genes were significantly differentially expressed in the 6-month post-exposure group. However, the lung gene expression profiles showed substantial changes in the crystalline silica exposed animals at both one-day and 6-month post-exposure. Specifically, there were a total of 325 genes significantly differentially expressed (fold change >1.5 and FDR p<0.05) at the one-day post-exposure group and 3348 genes significantly differentially expressed at the 6-month post-exposure. The data obtained from the present study demonstrated that crystalline silica inhalation exposure, under the conditions employed in the present study, resulted in significant changes in lung toxicity parameters and lung gene expression profile in the rats at both 1-day and 6-month post-exposure.本研究以大鼠为模型，探究年龄对Min-U-Sil 5结晶二氧化硅暴露诱导的肺毒性的影响（若存在）。作为研究的一部分，本研究测定了受试动物血液与肺部的全基因组基因表达谱变化。为明确年龄是否会影响机体对结晶二氧化硅（crystalline silica）暴露的肺部应答，实验选用两种不同年龄段的健康雄性F344大鼠。 本实验中，老年组大鼠于暴露时为12月龄，通过全身吸入方式分别暴露于空气或结晶二氧化硅（Min-U-Sil 5）中，暴露参数为15 mg/m³、每日6小时、连续5天。该老年组大鼠可模拟45至50岁的工人群体。 在结晶二氧化硅暴露后的两个时间节点（1天与6个月），对受试动物实施安乐死并检测其肺部炎症、细胞毒性及氧化应激应答情况。对支气管肺泡灌洗（bronchoalveolar lavage）的毒性相关参数（如氧化产物生成与炎症反应）进行分析后发现，与同时间点空气暴露的对照组大鼠相比，结晶二氧化硅暴露组大鼠的肺毒性出现显著变化。 血液基因表达谱方面，相较于对照组，暴露组在两个时间点的基因表达仅出现极细微的变化。具体而言，暴露后1天的组别未检测到显著差异表达基因（倍数变化（fold change）>1.5且错误发现率校正P值（FDR p-value）<0.05），暴露后6个月的组别仅存在6个显著差异表达基因。 然而，肺部基因表达谱则显示，暴露组大鼠在两个时间点均出现显著的表达变化。具体而言，暴露后1天的组别共检测到325个显著差异表达基因（倍数变化>1.5且错误发现率校正P值<0.05），暴露后6个月的组别则达到3348个。 本研究所得数据表明，在本实验采用的暴露条件下，结晶二氧化硅吸入暴露会导致大鼠在暴露后1天与6个月时的肺毒性参数及肺部基因表达谱出现显著改变。