肝X受体的激活减轻了胎盘内皮细胞中氧化醇诱导的功能障碍
Meekha George1, Hanna Helene Allerkamp1, Zhanat Koshenov2
1Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria.
Biochimica et biophysica acta. Molecular and cell biology of lipids
|February 18, 2024
概括
高水平的氧化胆固醇 (oxysterols) 破坏胎盘血管功能,增加妊娠并发症的风险. 用激动剂激活肝X受体 (LXR) 有望扭转这些对胎盘内皮细胞的有害影响.
科学领域:
- 产科和妇科 产科和妇科
- 血管生物学 血管生物学
- 内分泌学 在内分泌学.
背景情况:
- 胎盘血管平衡对于胎儿发育至关重要;干扰可能导致围产期发病率.
- 氧化胆固醇 (oxysterols) 水平升高与妊娠并发症,如妊娠期糖尿病 (GDM) 和孕前 (PE) 有关.
- 这些情况往往涉及到胎盘血管功能受损.
研究的目的:
- 为了研究特定氧化醇 (7-基托胆固醇,7β-胆固醇) 对胎盘内皮细胞 (fpEC) 功能的影响.
- 为了确定肝脏X受体 (LXR) 激活是否可以减轻氧化醇诱导的内皮功能障碍.
主要方法:
- 主要胎盘内皮细胞 (fpEC) 用氧化醇进行治疗.
- 测量包括反应性氧物种 (ROS) 生产,线粒体膜潜力,细胞内 (Ca2+) 水平,细胞结合完整性,膜刚性,血管透性和单细胞粘附.
- 使用T0901317 (TO) 对这些参数LXR激活的影响被评估.
主要成果:
- 氧醇增加了ROS的产生,使线粒体膜潜力脱极化,改变了Ca2+水平,重新组织了细胞结,增加了膜的刚性和透性,并在fpEC中增强了单细胞粘附.
- 激活LXR显著逆转了氧化诱导的ROS生成,单细胞粘附和细胞结交透性.
- 虽然没有统计学意义,但LXR激活显示出稳定调动的趋势.
结论:
- 系统性氧胆固醇升高与胎盘血管功能障碍有关.
- LXR激动剂在减轻氧对胎儿胎盘血管系统的不良影响方面显示出潜在的治疗价值.
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