发育调节的CYP2E1表达与胎儿肺转录反应与母亲的乙氨基暴露有关
Emma M Golden1, Zhuowei Li2, Lijun Zheng1
1Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Biomedicines
|October 29, 2025
概括
孕妇在怀孕期间暴露于乙氨基 (APAP) 可能会影响胎儿的肺部发育. 一项研究发现,在小鼠胚胎第18天接触APAP会引发与细胞压力和发育中的肺部炎症相关的显著基因表达变化.
科学领域:
- 发展性毒理学 发展性毒理学
- 药理学 药理学是指药理学的学科.
- 呼吸系统药物 呼吸系统药物
背景情况:
- 乙氨基 (APAP) 在怀孕期间被广泛使用.
- APAP暴露与儿童呼吸系统问题有关,但机制尚不清楚.
- APAP的新陈代谢涉及CYP2E1,一种酶,其肺部表达在胎儿肺部发育期间达到顶峰.
研究的目的:
- 为了调查肺部Cyp2e1表达的发育激增是否会在母体APAP暴露后触发胚胎肺部的转录反应.
- 评估APAP对与氧化应激,炎症和发育中的小鼠肺中的亡相关的基因表达的影响.
主要方法:
- 怀孕的小鼠在第17或第18个胚胎日接触到APAP.
- 分析了CYP2E1的基因表达,NRF2标和压力/亡标记物.
- 在暴露于E18 APAP后,对后代肺部进行了基因病理学检查.
主要成果:
- 母亲对E17的APAP暴露诱导了Cyp2e1,但显示出不一致的转录变化.
- 在E18暴露于APAP导致强大的诱导Cyp2e1,NRF2点,以及细胞亡,炎症和细胞应激的标记.
- 在E18 APAP暴露后,出生时没有观察到急性肺损伤.
结论:
- 发育调节的,剂量依赖的对母体APAP的转录反应发生在胚胎小鼠肺部.
- 转录变化并不一定表明直接的肺损伤;需要对蛋白质水平进行分析.
- 需要对APAP毒性和长期呼吸道结果中的发育调节的Cyp2e1进行进一步的研究.
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