Acrolein-induced transcriptomic alterations in male Wistar-Kyoto rats. Acrolein-induced transcriptomic alterations in male Wistar-Kyoto rats

Acute acrolein inhalation in male rats resulted in multi-tissue transcriptomic alterations that were observed through Illumina mRNA sequencing. Specifically, site-specific respiratory expression profile differences were noted between air- and acrolein-exposed groups. Nasal epithelial tissue demonstrated 452 differentially expressed genes (DEGs) (310 up-regulated and 142 down-regulated)and lung tissue demonstrated 95 DEGs (80 up-regulated and 15 down-regulated). Notable transcriptomic alterations were also observed in liver tissue of acrolein-exposed rats, with 1699 identified DEGs (788 up-regulated and 911 down-regulated). A variety of mRNA expression profile differences resulting from acute acrolein inhalation was observed in other peripheral tissues, including adipose, muscle, adrenals, hippocamus, and hypothalamus. Gene changes were largely representative of oxidative and inflammatory response in the nose, as well as xenobiotic metabolism changes in the lung. Liver changes, which were most numerous, included alterated metabolic signaling (Sirtuin and FXR signaling), as well as alterated oxidoreductive, GPCR, and glucocorticoid pathways. Together, these data demonstrate acrolein, a well-characterized respiratory irritant, induces systemic neuroendocrine immunological and metabolic stress. Overall design: Adult male Wistar-Kyoto rats were exposed to air (0ppm) or acrolein nose-only for 4hr total exposure duration. For the first 30 minutes of exposure, increasing half-log exposure concentrations were used at 0, 0.1, 0.316, and 1 ppm, such that each concentration was employed for 7.5 minutes, with this 30 minute window being followed by 3.5 hours at the highest concentration of acrolein of 3.16 ppm. Exposures were conducted ~0700-1100 AM and performed under general room temperature and humidity. Immediately after exposure, rats were necropsied, tissues collected and flash frozen in liquid nitrogen, and frozen for later analysis. Later, RNA was extracted and sequenced.

雄性大鼠经急性丙烯醛吸入染毒后，可引发多组织转录组学改变，该变化通过Illumina mRNA测序得以检测。具体而言，空气暴露组与丙烯醛暴露组间存在部位特异性的呼吸道表达谱差异。鼻上皮组织中共鉴定出452个差异表达基因（differentially expressed genes, DEGs），其中310个上调、142个下调；肺组织中鉴定出95个DEGs，80个上调、15个下调。丙烯醛暴露大鼠的肝脏组织中同样观测到显著的转录组改变，共鉴定出1699个DEGs，其中788个上调、911个下调。在其他外周组织（包括脂肪组织、肌肉、肾上腺、海马（hippocampus）和下丘脑）中，同样观测到急性丙烯醛吸入所导致的多种mRNA表达谱差异。
鼻部的基因变化主要反映氧化应激与炎症反应，而肺部的基因变化则体现为异生物质代谢相关改变。肝脏的基因变化数量最多，涵盖了Sirtuin信号通路与FXR信号通路等代谢信号通路的异常，以及氧化还原、G蛋白偶联受体（G protein-coupled receptor, GPCR）和糖皮质激素通路的改变。综上，这些数据表明，丙烯醛——一种已被充分表征的呼吸道刺激物——可诱发全身性的神经内分泌、免疫及代谢应激。

整体实验设计：成年雄性Wistar-Kyoto大鼠被暴露于空气（0 ppm）或仅经鼻腔吸入丙烯醛，总暴露时长为4小时。暴露的前30分钟，采用半对数递增的暴露浓度：0、0.1、0.316及1 ppm，每个浓度持续7.5分钟；随后的3.5小时维持最高浓度3.16 ppm的丙烯醛暴露。暴露实验于每日约7:00至11:00进行，实验环境为常规室温与湿度条件。染毒结束后立即对大鼠实施安乐死并剖检，采集组织并置于液氮中快速冷冻保存，待后续分析。后续提取组织总RNA并进行测序。