目的 文拉法辛是基于“神经递质假说”研发的抗抑郁药,在临床已广泛使用。笔者运用转录组学技术探究文拉法辛对慢性温和不可预知应激(CUMS)大鼠抗抑郁作用机制。方法 采用文拉法辛对CUMS动物模型进行干预,观察大鼠的行为学变化。同时采集大鼠海马组织,应用 RNA-seq技术对大鼠海马组织RNA进行转录组测序,并通过功能注释与富集分析其作用机制。结果 与模型组/空白组鉴定出的差异基因比较,发现文拉法辛回调的差异基因有387个,其中上调基因237个,下调基因150个。显著回调通路有26条,这些通路涉及昼夜节律、钙信号通路、γ-氨基丁酸能突触、神经活性配体-受体相互作用和5-羟色胺能突触等。文拉法辛可能通过调节这些通路上Adcy8、Camk2d、Gng4、Grin2a、Itpr1、Kcnj6、Rasd1、Chrna7、Erbb3、Atp2b1、Atp2b4、Htr2a、Htr2c、Htr5b、Ppp3ca和Trhr等发挥抗抑郁作用。结论 文拉法辛抗抑郁作用机制与调控神经系统、信号分子与相互作用和信号转到有关系,为进一步研究文拉法辛抗抑郁的作用奠定基础。
Abstract
OBJECTIVE To explore the antidepressant mechanism of venlafaxine on the chronic mild unpredictable stress (CUMS) rat using transcriptomics technology. METHODS CUMS program was used to model rats, and venlafaxine was used as an intervention drug. RNA-seq technology was used to perform transcriptome of rat hippocampal RNA sequencing. Through functional annotation and enrichment analysis, screening gene expression signaling pathway of CUMS rats after administration in the venlafaxine group. RESULTS Compared with the differential genes identified in the model group vs normal control group, it was found that there are 387 differential genes, including 237 up-regulated genes and 150 down-regulated genes, and 26 significant pathways callback by venlafaxine. These pathways involve circadian entrainment, calcium signaling pathway, GABAergic synapse, neuroactive ligand-receptor interaction and serotonergic synapse, etc. Venlafaxine may exert antidepressant effects by regulating Adcy8, Gad1, Gad2, Htr2a, Chrna7, Erbb3, Map4k4, Nr4a1, Zfpm2, LOC100911372, Twist1, Ntng1, Robo3 and Slit2, etc. on these pathways. CONCLUSION The mechanism of venlafaxine's antidepressant may be related to the regulation of nervous system, signaling molecules and interaction and signal transduction, which lays the foundation for further research on the antidepressant effect of venlafaxine.
关键词
文拉法辛 /
抑郁症 /
海马组织 /
转录组学 /
富集分析
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Key words
venlafaxine /
depression /
hippocampus /
transcriptome /
enrichment analysis
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参考文献
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脚注
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基金
山西省科技计划项目资助(201903D321210)
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