Wang Yiliang, Li Nu, Chen Xiaoyu, Zhao Yue, Qu Letian, Cai Dasheng
Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.
Department of Health Statistics, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, People's Republic of China.
Cell Biol Toxicol. 2024 Dec 21;41(1):13. doi: 10.1007/s10565-024-09964-4.
The use of anesthetics during surgery can cause severe neurological damage and cognitive dysfunction in elderly patients. However, this health issue currently lacks corresponding therapeutic strategies. This research involved the utilization of single-cell RNA sequencing (scRNA-seq) and transcriptomic assessment to pinpoint crucial cell classifications and molecular pathways, as well as the lncRNA expression profiles, that undergo substantial alterations in aged rats experiencing sevoflurane-induced cognitive impairment. The results of our investigation pointed towards the enrichment of differentially expressed genes in neurons within the Nrf2/ARE signaling pathway, alongside an elevated expression of lncRNA NEAT1. Subsequently, by constructing a rat model to induce neuronal dysfunction with sevoflurane and performing experiments both in vivo and in vitro (including TUNEL staining, H&E staining, immunohistochemistry, immunofluorescence, and flow cytometry to assess apoptosis levels), we confirmed that NEAT1 inhibits the Nrf2/ARE/HO-1 pathway-related factors. Sevoflurane promotes oxidative stress and apoptosis in primary hippocampal neurons through the NEAT1/Nrf2/ARE/HO-1 axis. This study elucidates the molecular mechanism by which sevoflurane induces hippocampal neuronal damage and cognitive decline in elderly rats via the regulation of the lncRNA NEAT1/Nrf2 signaling axis. We discovered that upregulation of NEAT1 suppresses the Nrf2 signaling pathway, further inducing neuronal damage and cognitive dysfunction, furnishing an essential citation to grasp the molecular pathways involved in neuronal harm and devising corresponding treatment methodologies.
手术期间使用麻醉剂会导致老年患者出现严重的神经损伤和认知功能障碍。然而，这一健康问题目前缺乏相应的治疗策略。本研究利用单细胞RNA测序（scRNA-seq）和转录组评估来确定在经历七氟醚诱导的认知障碍的老年大鼠中发生显著改变的关键细胞类别、分子途径以及lncRNA表达谱。我们的研究结果表明，Nrf2/ARE信号通路中的神经元中差异表达基因富集，同时lncRNA NEAT1表达升高。随后，通过构建七氟醚诱导神经元功能障碍的大鼠模型并进行体内和体外实验（包括TUNEL染色、H&E染色、免疫组织化学、免疫荧光和流式细胞术以评估凋亡水平），我们证实NEAT1抑制Nrf2/ARE/HO-1通路相关因子。七氟醚通过NEAT1/Nrf2/ARE/HO-1轴促进原代海马神经元的氧化应激和凋亡。本研究阐明了七氟醚通过调节lncRNA NEAT1/Nrf2信号轴诱导老年大鼠海马神经元损伤和认知衰退的分子机制。我们发现NEAT1的上调抑制Nrf2信号通路，进一步诱导神经元损伤和认知功能障碍，为理解神经元损伤所涉及的分子途径和设计相应的治疗方法提供了重要依据。
