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孕产妇的MitoQ治疗对由于产前德克萨米他的CYP活动的编程变化具有保护性

Millicent G A Bennett¹, Ashley S Meakin¹, Kimberley J Botting-Lawford²

¹Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Science, University of South Australia, Adelaide, SA 5000, Australia.

|March 27, 2025

概括

产前皮质类固醇 (ACS) 降低了胎儿肝脏药物代谢酶,但将ACS与抗氧化剂MitoQ结合起来可以防止后代的长期变化. 单独使用MitoQ可以提高一些酶活性和抗氧化剂标记物.

科学领域:

药理学和毒理学药理学和毒理学
发育生物学发展生物学
孕产妇和胎儿医学孕产妇和胎儿医学

背景情况:

产前皮质类固醇 (ACS) 用于加快胎儿的肺成熟,在怀孕中有早产风险.
ACS可能会引起副作用,包括氧化应激,可能会改变细胞染色体P450 (CYP) 酶活性.
ACS对胎儿发育和后代的长期肝脏药物代谢的影响需要进一步研究.

研究的目的:

研究抗氧化剂对ACS诱导的胎儿肝脏CYP活性变化的保护作用.
确定母体治疗 (ACS,抗氧化剂MitoQ或组合) 对后代肝脏药物代谢酶的影响.
评估暴露于产前治疗的羔羊肝CYP活动的长期编程.

主要方法:

孕妇被分配给接受盐水,甲 (Dex; ACS),MitoQ (抗氧化剂) 或Dex+MitoQ.
肝脏CYP活性和蛋白质丰度在胎儿和9个月大的羔羊中使用功能测试和西欧斑块进行测量.
在特定的妊娠期内给予母亲治疗,并在产期和之后评估后代.

主要成果:

在9个月大的羊羔中,甲松 (Dex) 降低了胎儿的CYP3A活性,并降低了多个肝脏CYP活动 (CYP1A2,CYP2B6,CYP2C8,CYP2E1).
德克斯和MitoQ的组合改善了后代的CYP活性降低,恢复了大多数酶的水平控制.
单独MitoQ增加了CYP2B6和CYP3A的活性,并增强了羊羔的催化酶 (CAT) 表达;所有治疗都影响了线粒体分裂调节器.

结论:

在产前暴露于德克萨米他 (Dex) 会导致年轻成年后代的肝脏CYP活性有计划的减少.
同时使用抗氧化剂MitoQ和Dex可减轻这些对药物代谢酶的长期不良影响.
抗氧化剂可能在保护胎儿发育免受ACS治疗的意外后果方面发挥作用.

关键词:

在产前使用皮质类固醇.抗氧化剂是一种抗氧化剂.细胞染色体p450的产物.健康规划中的健康规划.肝脏肝脏肝脏肝脏肝脏肝脏后代的后代是一个后代.怀孕怀孕怀孕怀孕怀孕过早分娩过早分娩是什么

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