葡萄糖皮质类药物诱导了不适应性上皮质应激反应,使急性损伤恶化
Luping Zhou1,2,3, Marc Torres Pereiro1, Yanqun Li2,3
1Institute of Pharmacology, University of Marburg, Karl-von-Frisch-Straße 2, Marburg 35043, Germany.
Science translational medicine
|October 2, 2024
概括
在严重的COVID-19病例中,从狂犬病溶解中产生的肌球蛋白会通过破坏管状上皮细胞引起急性损伤 (AKI). 葡萄糖皮质醇受体的激活会使这种损伤恶化,阻碍脏的修复.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 分子生物学分子生物学
- 病理生理学 病理生理学
背景情况:
- 急性损伤 (AKI) 是一个重要的临床问题,特别是在重症COVID-19患者中.
- 管状上皮细胞 (TEC) 是AKI的核心,但其适应和不适应的机制尚不清楚.
- 肌球蛋白诱导的TEC损伤与严重的COVID-19期间的AKI有关.
研究的目的:
- 阐明AKI中TEC适应不良的分子机制.
- 研究葡萄糖皮质体受体 (GR) 信号在AKI病理生理学中的作用.
- 为了确定德克萨米他对AKI的影响.
主要方法:
- 来自COVID-19患者的尸检队列的分析.
- 实验使用人类脏活检,小鼠模型 (肌红素,仁胺诱导,叶酸诱导的AKI),小鼠脏管体和人类脏切片培养物.
- 对DNA修复,细胞信号和线粒体功能的分子分析.
主要成果:
- 在狂犬病解剖过程中释放的肌球蛋白是严重的COVID-19中TEC损伤和AKI的关键原因.
- 由内源性和外源性葡萄糖皮质体 (德甲) 激活葡萄糖皮质体受体会加剧管道损伤.
- 在TEC中GR信号传递促进了不适应的转录程序,损害了DNA修复和线粒体功能.
结论:
- 葡萄糖皮质体受体激活是推动TEC在AKI中的不适应的一个关键机制.
- 准GR信号可能为AKI提供治疗策略.
- 这项研究揭示了一种新的途径,该途径在严重的COVID-19中导致损伤.
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