Effect of Dexmedetomidine on ncRNA and mRNA Profiles of Cerebral Ischemia-Reperfusion Injury in Transient Middle Cerebral Artery Occlusion Rats Model

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX's therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham (S) and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO+DEX (I/R+DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX's efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX's neuroprotective mechanisms and its clinical applications.缺血性脑卒中（Ischemic stroke）是一类造成全球沉重健康负担的疾病，快速血管再通治疗虽为临床关键干预手段，但往往难以有效缓解缺血再灌注（ischemia-reperfusion, I/R）损伤。右美托咪定（Dexmedetomidine, DEX）已被证实可减轻脑I/R损伤，但其潜在分子机制，尤其是与非编码RNA（non-coding RNAs, ncRNAs）的相互作用，仍未完全阐明。本研究旨在探讨右美托咪定减轻脑I/R损伤的治疗效应及潜在分子机制。研究通过建立成年大鼠短暂性大脑中动脉闭塞（transient middle cerebral artery occlusion, tMCAO）模型以模拟脑I/R损伤，并于缺血前及再灌注后给予右美托咪定干预。对缺血侧大脑皮层样本进行RNA测序及生物信息学分析，以筛选差异表达的非编码RNA及mRNA。测序结果显示，假手术组（sham, S）与tMCAO再灌注组（I/R）间共鉴定出6494个差异表达mRNA及2698个差异表达环状RNA（circRNA）；I/R组与tMCAO+右美托咪定干预组（I/R+DEX）间则鉴定出1809个差异表达长链非编码RNA（lncRNA）、763个差异表达mRNA及2795个差异表达circRNA。基因本体（Gene Ontology, GO）分析显示，差异表达基因显著富集于多细胞生物发生、细胞膜组分及蛋白质结合功能条目。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）分析进一步揭示了右美托咪定减轻脑I/R损伤的潜在作用机制，其核心基因主要参与炎症相关信号通路。本研究证实了右美托咪定可有效减轻脑I/R损伤，为其在缺血性脑卒中中的脑保护作用提供了新的理论依据。未来仍需开展深入研究以全面阐明右美托咪定的神经保护机制及其临床应用前景。