Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Sci Rep. 2024 Oct 23;14(1):25108. doi: 10.1038/s41598-024-75875-3.
Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.
心脏停搏后脑(PCABI)是一种严重的医疗状况,其特征是存在显著的神经功能障碍和死亡风险。然而,其发展的具体过程和关键分子尚不完全清楚。基于竞争内源性 RNA(ceRNA)的分析已被涉及到神经紊乱的发生和进展,但其在 PCABI 中的作用仍不清楚。在这项研究中,我们对心脏停搏和心肺复苏(CA/CPR)大鼠模型进行了 RNA 转录组测序分析,以鉴定差异表达的基因。使用 miRWalk 2.0 和 Cytoscape 中的 Cytohubba 插件构建了 ceRNA 调控网络。随后,通过实时定量逆转录聚合酶链反应和双荧光素酶活性测定验证了 MSTRG.13,871、miR-155-5p 和 Grip1 在 CA/CPR 组中差异表达,并且 MSTRG.13,871 能够靶向 miR-155-5p 和 Grip1。基因本体论和京都基因与基因组百科全书分析显示,ceRNA 网络在免疫调节机制中富集,如线粒体、凋亡过程和细胞死亡的负调控。我们的研究通过揭示大鼠心脏停搏后海马 CA1 区涉及 MSTRG.13,871-miR-155-5p-Grip1 的关键调控轴,强调了 PCABI 的发病机制,为设计创新疗法提供了可行的控制机制,可能作为理论基础。