慢性炎性痛模型小鼠腹外侧眶额叶皮质的转录组分析  

Transcriptomic analysis of ventrolateral orbitofrontal cortex in chronic inflammatory pain model mice

作　　者：张思博 尹美娴 李婧[1] 柳垂亮[1] ZHANG Sibo;YIN Meixian;LI Jing;LIU Chuiliang(Foshan Clinical Medicine School,Guangzhou University of Chinese Medicine,Foshan 528000;Department of Anatomy and Neurobiology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]广州中医药大学佛山临床医学院,佛山528031 [2]中山大学中山医学院人体解剖学与生理系,广州510080

出　　处：《神经解剖学杂志》2024年第2期187-195,共9页Chinese Journal of Neuroanatomy

基　　金：佛山市科技创新项目(FS0AA-KJ218-1301-0041)。

摘　　要：目的:筛选小鼠腹外侧眶额皮质(vlOFC)参与疼痛调节的生物学标记物。方法:雄性C57BL/6J小鼠于左后足底注射完全弗氏佐剂(CFA)诱导慢性炎性痛。通过测定缩足阈值(PWT)和缩足潜伏期(PWL)检测痛敏变化。行为学测试之后取小鼠vlOFC新鲜组织进行转录组测序。运用生物信息学方法筛选差异表达基因(DEGs),并进行生物学功能和通路富集分析。结果:与PBS组小鼠相比,CFA组小鼠左后足机械痛阈值和热痛导致的缩爪潜伏期均显著降低(P<0.001)。两组小鼠vlOFC的DEGs为497个,其中上调143个,下调354个。基因本体(GO)和京都基因与基因组百科全书(KEGGs)分析显示:慢性炎性痛模型小鼠,vlOFC的DEGs主要表现在有机阳离子转运、神经递质转运、胞质钙离子浓度的调节等生物过程;与G蛋白偶联受体(GPCRs)、神经肽相关以及铵转运等分子功能相关;DEGs主要集中于神经活性配体-受体相互作用、细胞因子-细胞因子受体相互作用、cAMP信号通路。Reactome功能富集分析显示,参与富集的DEGs数量最多且校正后P值最低的通路为GPCRs配体结合。结论:vlOFC中的离子转运、神经递质转运与结合、GPCRs相关活动参与了慢性炎性痛的调节。Objective:Biological markers of the ventrolateral orbitofrontal cortex(vlOFC)involved in pain regulation were screened.Methods:Chronic inflammatory pain was induced in male C57BL/6J mice by injection of complete Freund’s adjuvant(CFA)into the left posterior plantar.Paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were detected to evalue hyperalgesia.Transcriptome sequencing was performed on fresh tissue from vlOFC of mice after behavioral tests.The differentially expressed genes(DEGs)were screened by bioinformatics method,and their biological functions and pathways were enriched.Results:Compared with the PBS group,the left hindpaw mechanical pain threshold and the paw withdrawal latency caused by heat pain were significantly reduced in the CFA group(P<0.001).The DEGs of vlOFC in the two groups were 497,of which 143 were up-regulated and 354 were down-regulated.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGGs)analysis showed that:In chronic inflammatory pain model mice,DEGs of vlOFC were mainly manifested in biological processes such as organic cation transport,neurotransmitter transport,and regulation of cytoplasmic calcium ion concentration.It is related to G protein-coupled receptors(GPCRs),neuropeptides and ammonium transport.DEGs mainly focuses on neuroactive ligand-receptor interactions,cytokine-cytokine receptor interactions,and cAMP signaling pathways.Reactome functional enrichment analysis showed that the pathway with the highest number of DEGs enriched and the lowest P value-adjusted was GPCRs ligand binding.Conclusion:Ion transport,neurotransmitter transport and binding,and GPCRs-related activities in vlOFC are involved in the regulation of chronic inflammatory pain.

关 键 词：慢性炎性痛 腹外侧眶额叶皮质 转录组分析 小鼠 

分 类 号：R402[医药卫生—临床医学] R-332