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.雄性大鼠经急性丙烯醛吸入染毒后，出现多组织转录组学改变，该变化通过Illumina mRNA测序得以观测。具体而言，空气暴露组与丙烯醛暴露组之间存在呼吸道特定部位的基因表达谱差异。鼻上皮组织中鉴定出452个差异表达基因（differentially expressed genes, DEGs），其中上调基因310个、下调基因142个；肺组织中则鉴定出95个DEGs，上调基因80个、下调基因15个。丙烯醛暴露大鼠的肝组织中同样观测到显著的转录组学改变，共鉴定出1699个DEGs，其中上调基因788个、下调基因911个。急性丙烯醛吸入还在其他外周组织中引发了多种mRNA表达谱差异，涉及的组织包括脂肪组织、肌肉、肾上腺、海马体以及下丘脑。鼻部的基因变化主要反映了氧化应激与炎症反应，而肺部的基因变化则与外源性物质代谢改变相关。数量最多的肝脏基因变化则涉及代谢信号通路（Sirtuin信号通路与法尼醇X受体（FXR）信号通路）的异常，以及氧化还原、G蛋白偶联受体（GPCR）和糖皮质激素通路的改变。综上，这些数据表明，作为一种已被充分研究的呼吸道刺激物，丙烯醛可引发全身性的神经内分泌、免疫及代谢应激。