孕产前母亲对索福斯布维尔的暴露会影响产前胎儿组织中的线粒体生物发生:对大鼠的实验研究
Shimaa A Mahmoud1, Maryam M Abdel-Aziz2, Rana H M Khafaga2
1Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt. shimaa.abdelraheem@alexu.edu.eg.
Molecular medicine (Cambridge, Mass.)
|June 6, 2023
概括
怀孕前母亲接触索福斯布维尔可能会对胎儿发育产生负面影响. 暴露于大鼠中的索福斯布维尔减少了胎儿肝脏和肌肉中的线粒体DNA,但在胎盘组织中增加了它.
科学领域:
- 生殖生物学 生殖生物学
- 药理学 药理学是指药理学的学科.
- 线粒体生物学 线粒体生物学
背景情况:
- 型肝炎病毒 (HCV) 感染是一个全球性的健康问题,埃及的患病率最高.
- 全球努力的目标是到2030年消除HCV.
- 索福斯布维尔是HCV的关键抗病毒药物,但它的胎盘转移是从动物研究中知道的.
研究的目的:
- 为了研究孕产前母亲对Sofosbuvir暴露对线粒体生物发生的影响.
- 评估对胎儿肝脏,骨肌肉和胎盘组织的影响.
主要方法:
- 雌性大鼠被暴露于Sofosbuvir (4毫克/公斤/天) 或安慰剂3个月.
- 诱导怀孕,并在妊娠第17天收集组织.
- 分析了线粒体DNA拷贝数和关键生物发生因子.
主要成果:
- 索福斯布维尔暴露减少了胎儿肝脏 (24%) 和肌肉 (29%) 中的线粒体DNA拷贝数.
- 关键的线粒体生物发生因子 (PGC-1α,NRF-1,TFAM) 在胎儿组织下调.
- 胎盘组织显示线粒体DNA复制数增加 (43%).
结论:
- 预先设想 Sofosbuvir暴露可能会对怀孕结果产生不利影响.
- 该药物可能会通过改变线粒体平衡来损害胎盘和胎儿器官的发育.
- 需要进一步的研究来了解长期影响.
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