Wang Yujie, Qian Min, Qu Yinyin, Yang Ning, Mu Bing, Liu Kaixi, Yang Jing, Zhou Yang, Ni Cheng, Zhong Jing, Guo Xiangyang
Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Aging Neurosci. 2020 May 7;12:122. doi: 10.3389/fnagi.2020.00122. eCollection 2020.
Previous studies have shown multiple mechanisms and pathophysiological changes after anesthesia, and genome-wide studies have been implemented in the studies of brain aging and neurodegenerative diseases. However, the genome-wide gene expression patterns and modulation networks after general anesthesia remains to be elucidated. Therefore, whole transcriptome microarray analysis was used to explore the coding gene expression patterns in the hippocampus of aged rats after sevoflurane anesthesia. Six hundred and thirty one upregulated and 183 downregulated genes were screened out, then 44 enriched terms of biological process, 16 of molecular function and 18 of the cellular components were identified by Gene Ontology (GO) and KEGG analysis. Among them, oxidative stress, metabolism, aging, and neurodegeneration were the most enriched biological processes and changed functions. Thus, involved genes of these processes were selected for qPCR verification and a good consistency was confirmed. The potential signaling pathways were further constructed including mitochondrion and oxidative stress-related ---- signaling, multiple metabolism signaling (, -, - and ), as well as aging and neurodegeneration related signaling (--- and ). These results provide potential therapeutic gene targets for brain function modulation and memory formation process after inhaled anesthesia in the elderly, which could be valuable for preventing postoperative brain disorders and diseases, such as perioperative neurocognitive disorders (PND), from the genetic level in the future.
先前的研究已经表明麻醉后存在多种机制和病理生理变化,并且全基因组研究已应用于脑衰老和神经退行性疾病的研究中。然而,全身麻醉后的全基因组基因表达模式和调控网络仍有待阐明。因此,本研究采用全转录组微阵列分析来探究老年大鼠七氟醚麻醉后海马体中编码基因的表达模式。筛选出631个上调基因和183个下调基因,然后通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析鉴定出44个生物过程富集术语、16个分子功能富集术语和18个细胞成分富集术语。其中,氧化应激、代谢、衰老和神经退行性变是最富集的生物过程和变化的功能。因此,选择这些过程中涉及的基因进行qPCR验证,并证实了良好的一致性。进一步构建了潜在的信号通路,包括线粒体和氧化应激相关的----信号通路、多种代谢信号通路(、、和),以及衰老和神经退行性变相关的信号通路(---和)。这些结果为老年患者吸入麻醉后脑功能调节和记忆形成过程提供了潜在的治疗基因靶点,这对于未来从基因水平预防术后脑部疾病,如围手术期神经认知障碍(PND),可能具有重要价值。