选择性血清素再吸收抑制剂通过线粒体和肉类粒体的功能障碍诱导心脏毒性
Yawei Shen1,2,3, Cameron E Brown1,2, Xiao Li1,2
1Department of Biological Sciences, Clemson University, Clemson, SC, USA.
Communications biology
|May 12, 2025
概括
选择性血清素再吸收抑制剂 (SSRI) 通过损害线粒体功能和瘤细胞结构,损害发育中的心肌细胞. 这项研究揭示了SSRI.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 选择性血清素再吸收抑制剂 (SSRI) 在怀孕期间通常被处方.
- 母亲使用SSRI与新生儿先天性心脏缺陷的风险增加有关.
- 导致SSRI引起的心脏毒性的确切机制仍然不完全理解.
研究的目的:
- 研究SSRI对心脏发育和功能的毒性影响.
- 阐明SSRI诱导心脏毒性的潜在分子机制.
- 评估特定的SSRI (fluoxetine,paroxetine,sertraline) 对心肌细胞的影响.
主要方法:
- 利用人类多能干细胞创建2D单层心肌细胞和3D心脏器官模型.
- 评估了SSRI暴露对心肌细胞分化,线粒体功能和瘤组织的影响.
- 在有机体模型中量化ATP生产,线粒体呼吸,评估心脏发育和血管生成.
主要成果:
- 暴露于SSRI显著抑制了ATP的产生和线粒体呼吸在分化心肌细胞.
- 观察到线粒体平衡和瘤细胞结构的破坏,导致心肌细胞功能障碍.
- 心脏器官模型显示线粒体呼吸减少,ATP产生受损,以及对心脏发育和血管生成的潜在影响.
结论:
- 在发育中的心肌细胞中,SSRI诱导线粒体功能障碍和体组织失调.
- 这些细胞缺陷凸显了与SSRI暴露相关的胎儿心脏系统的潜在风险.
- 这些发现强调需要进一步调查怀孕期间的SSRI安全性.
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