经典的阿佐尔抗真菌药物影响人类胎盘模型中的类固醇活性
Line Mathiesen1, Lisa Hoyng Alstrup2, Stine Buchholdt2
1Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Pharmacological research
|August 31, 2025
概括
在怀孕期间使用的阿佐尔抗真菌药物 (AAD) 穿过胎盘并通过抑制芳香酶来破坏胎盘激素的产生. 这会影响胎儿的暴露和内分泌功能,对孕妇的健康有影响.
科学领域:
- 药理学
- 内分泌学
- 生殖生物学
背景情况:
- 怀孕期间的阴道角膜炎可能会导致并发症.
- 类抗真菌药物 (AAD) 是常见的治疗方法,但被怀疑是内分泌干扰剂.
- 研究AADs的胎盘转移和内分泌作用对于孕产妇和胎儿的健康至关重要.
研究的目的:
- 评估胎儿暴露于ADS.
- 评估ADS对人类胎盘的内分泌干扰作用.
- 了解AADs对胎盘类固醇生成的影响.
主要方法:
- 人体体内的胎盘 perfusion 模型.
- 液体染色体-双重质谱 (LC-MS/MS) 用于量化AAD和类固醇.
- 质谱成像和AAD分布和酶相互作用的分子对接.
主要成果:
- 其他抗体 (miconazole,clotrimazole,fluconazole) 很容易通过胎盘.
- 在胎盘组织中积累了miconazole和clotrimazole;在胎盘中,fluconazole达到母体剂量的50%.
- 药物抑制了胎盘的芳酶活性,增加了雄激素和降低了雌激素,而伊米达比可纳更强.
结论:
- AADs通过胎盘传递并影响胎盘内分泌.
- 由ADS抑制胎盘芳分酶是一个关键的内分泌干扰作用.
- 需要进一步研究以了解对胎儿发育的长期影响.
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