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七氟醚通过海马体中 NMDA 受体上调神经元死亡过程相关的 Ddit4 表达。

Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus.

机构信息

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 100021, China.

出版信息

Aging (Albany NY). 2023 Jun 21;15(12):5698-5712. doi: 10.18632/aging.204822.

DOI:10.18632/aging.204822
PMID:37348034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10333074/
Abstract

Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, , , , and are related to the neuronal death process. We further confirmed that these genes, especially , were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. , the core target receptor of sevoflurane, rather than , mediates the sevoflurane regulation of expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal as a potential target mediated by , which may provide a new target for the treatment of sevoflurane neurotoxicity.

摘要

术后认知功能障碍(POCD)是麻醉和手术引起的一种严重且常见的并发症。全身麻醉神经毒性诱导的神经元凋亡是一个高危因素。然而,对于全身麻醉调节的基因表达模式的综合分析以及对分子机制的进一步研究还很缺乏。在这里,我们对 GEO 数据库中 GSE139220 中接受七氟醚麻醉的老年大鼠海马体的基因表达进行了生物信息学分析,共发现 226 个差异表达基因(DEGs),并根据基因富集的生物学过程数量对枢纽基因进行了研究,并在 Cytoscape 中的 cytoHubba 中使用 12 种算法进行了筛选。在筛选出的枢纽基因中,、、、和 与神经元死亡过程有关。我们进一步证实,这些基因,尤其是 ,在接受七氟醚麻醉的老年小鼠海马体中上调。而不是 ,作为七氟醚的核心靶受体,介导了 表达的七氟醚调节。我们的研究筛选出了七氟醚调节的 DEGs,并关注神经元死亡过程,揭示 作为一个潜在的由 介导的靶标,这可能为治疗七氟醚神经毒性提供一个新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/4f2c809977e1/aging-15-204822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/44bd4d966a6d/aging-15-204822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/148150f3950c/aging-15-204822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/7ed1bef44365/aging-15-204822-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/80b4debd2162/aging-15-204822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/df33cf3ab1f0/aging-15-204822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/4f2c809977e1/aging-15-204822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/44bd4d966a6d/aging-15-204822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/148150f3950c/aging-15-204822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/7ed1bef44365/aging-15-204822-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/80b4debd2162/aging-15-204822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/df33cf3ab1f0/aging-15-204822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb6f/10333074/4f2c809977e1/aging-15-204822-g006.jpg

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