德克萨米他松,雷姆迪西维尔和阿兹罗米辛在肺上皮细胞中调节ACE2和IL-6
Gudrun Sigrid Ulrich-Merzenich1, Anastasiia Shcherbakova1, Carmen Pizarro2
1Medical Clinic III, AG Synergy Research and Experimental Medicine, University Hospital Bonn, Bonn, Germany.
Pneumologie (Stuttgart, Germany)
|September 16, 2024
概括
甲 (DEX) 在炎症期间增加肺细胞中的 ангиотензин转化酶2 (ACE2) 表达,可能增强SARS-CoV-2的进入. 然而,DEX也显著降低了炎症标志物IL-6.
科学领域:
- * 肺医学和病毒学研究.
- *对药物对肺细胞影响的体外和体内分析.
背景情况:
- *在COVID-19患者中最佳使用类固醇仍然是一个临床挑战.
- *目前的指导方针建议使用德克萨米他 (DEX) 进行呼吸辅助,但其精确的机制需要进一步阐明.
- * 调查DEX,雷姆迪西维尔 (RD) 和阿齐思罗米 (AZ) 对炎症和病毒进入途径的影响至关重要.
研究的目的:
- * 为了研究德克萨米他松 (DEX),雷梅西维尔 (RD) 和亚胺素 (AZ) 对肺细胞中脂多糖 (LPS) 诱导的炎症的影响.
- *分析对这些药物的反应中的 ангиотензин转化酶2 (ACE2) 和IL-6的表达.
- *通过检查公开可用的数据集来了解体内相关性.
主要方法:
- *采用人类支气管 (Calu) 和肺膜 (A549) 肺上皮细胞进行DEX,AZ或RDV加LPS.治疗的体外研究.
- *测量ACE2和IL-6以及IL-6蛋白释放的基因表达 (GE).
- *分析来自COVID-19患者肺组织和药物治疗肺细胞的公共基因表达数据集.
主要成果:
- *DEX在LPS刺激的肺细胞中增加了ACE2基因表达,而RDV和AZ则减少了ACE2基因表达.
- *DEX显著降低了膜细胞中LPS诱导的IL-6释放.
- *数据库分析表明,体内DEX治疗增加了ACE2的趋势,而COVID-19感染与较低的ACE2表达相关.
结论:
- * 甲可以在炎症期间提高肺细胞中ACE2表达的调节,这可能会增加SARS-CoV-2的进入.
- * 同时,DEX通过降低IL-6水平,显示出抗炎作用.
- *体内数据表明这些观察到的DEX对ACE2的影响,患者可能发生炎症.
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