微RNA引导的药物发现,以缓解COVID-19重症幸存者的持续性肺部并发症:一项纵向试点研究
María C García-Hidalgo1,2, Iván D Benítez1,2, Manel Perez-Pons1,2
1Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.
British journal of pharmacology
|February 15, 2024
概括
持续性肺功能障碍影响了超过一半的危急COVID-19幸存者. 这项研究确定了两个与这种疾病相关的微RNA (miRNA),为长期COVID肺部并发症的新疗法提供了潜在的点.
科学领域:
- 分子生物学分子生物学
- 肺部病理学 肺部病理学
- 病毒学 病毒学
背景情况:
- SARS-CoV-2 感染 (PASC) 后急性后续症状对全球健康构成挑战.
- 近50%的危急COVID-19幸存者经历了持续的肺部异常.
- 对PASC肺部并发症的分子机制和治疗方法的理解是有限的.
研究的目的:
- 调查COVID-19幸存者的持续性肺部并发症的分子基础.
- 为了确定与长期肺功能障碍相关的特定微RNA (miRNA).
- 探索PASC相关肺部疾病的潜在治疗点.
主要方法:
- 对119名危急COVID-19幸存者的长度研究,在短期和长期随访时对肺部进行评估.
- 使用RT-qPCR进行血miRNA分析,结合机器学习特征选择和生物信息分析.
- 使用独立的RNA测序和蛋白质组数据集进行验证.
主要成果:
- 84%的幸存者有短期的肺扩散受损,54.4%在一年后仍然受到影响.
- 两个miRNAs,miR-9-5p和miR-486-5p被确定为持续性肺功能障碍的关键参与者.
- 下游分析揭示了炎症,血管生成,细胞衰老,迁移和组织修复中的丰富途径.
结论:
- 揭示了早期机制性途径,这些途径有助于危急COVID-19幸存者的持续性肺功能障碍.
- 已识别的miRNA和途径为开发PASC的疾病修饰剂提供了有希望的目标.
- 对长期COVID肺部并发症的miRNA治疗方法的进一步研究是有必要的.
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