上海口腔医学

上海口腔医学 ›› 2023, Vol. 32 ›› Issue (1): 33-39.doi: 10.19439/j.sjos.2023.01.007

• 论著 • 上一篇    下一篇

大鼠三叉神经病理性疼痛致病关键转录分子分析

刘玥旻, 柴盈, 魏文斌, 刘芷扬, 韩孜祥, 陈敏洁   

  1. 上海交通大学医学院附属第九人民医院 口腔外科,上海交通大学口腔医学院,国家口腔医学中心, 国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011
  • 收稿日期:2021-09-02 修回日期:2021-12-10 出版日期:2023-02-25 发布日期:2023-06-12
  • 通讯作者: 陈敏洁,E-mail: chenmj_9hospital@126.com
  • 作者简介:刘玥旻(1996-),女,在读硕士研究生,E-mail: ashleyliu1996@163.com
  • 基金资助:
    上海市科委生物医学创新研究专项（21Y11903500）; 上海交通大学医学院附属第九人民医院罕见病注册登记项目（JYHJB202204）; 上海交通大学医学院附属第九人民医院临床研究型MDT项目（201701018）

Analysis of potential pathogenic factors of trigeminal neuralgia in rats

LIU Yue-min, CHAI Ying, WEI Wen-bin, LIU Zhi-yang, HAN Zi-xiang, CHEN Min-jie   

  1. Department of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine;; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011, China
  • Received:2021-09-02 Revised:2021-12-10 Online:2023-02-25 Published:2023-06-12

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摘要： 目的: 分析三叉神经病理性疼痛致病关键转录分子,筛选参考三叉神经痛发病的关键分子。方法: 构建大鼠三叉神经病理性疼痛模型,即眶下神经慢性缩窄环模型（chronic constriction injury of distal infraorbital nerve , IoN-CCI）,观察动物行为并收集三叉神经节进行RNA-seq转录组学分析。采用StringTie对基因组表达进行注释和定量,进一步计算基因和转录本的FPKM。使用DESeq2进行组间比较,设置筛选条件为P<0.05和差异倍数（fold change）>2及<0.5,筛选差异基因,采用火山图和聚类图进行展示。应用clusterProfiler软件对差异基因进行GO功能富集分析。结果: 术后第5天（POD5）,大鼠抓挠面部行为上升达到峰值;术后第7天（POD7）,von-frey值降到最低,提示大鼠机械痛阈值明显下降。RNA-seq分析IoN-CCI大鼠神经节,发现显著上调的信号通路包括B细胞受体信号通路、细胞黏附、补体及凝血级联通路;显著下调通路为系统性红斑狼疮相关调控通路;Cacna1s、Cox8b、Myl1、Ckm、Mylpf、Myoz1和Tnnc2等多个基因参与介导三叉神经痛的发生。结论: B细胞受体信号通路、细胞黏附、补体及凝血级联通路、神经免疫通路与三叉神经痛的发生密切相关。Cacna1s、Cox8b、Myl1、Ckm、Mylpf、Myoz1和Tnnc2等多个基因的相互作用,导致三叉神经痛发生。

关键词: 三叉神经痛, 转录组测序, 神经病理性疼痛

Abstract: PURPOSES: Transcriptomics-based analysis of key transcriptional molecules in the pathogenesis of trigeminal neuropathic pain was conducted to screen key molecules in the pathogenesis of trigeminal neuralgia. METHODS: Rat trigeminal nerve pathological pain model, namely chronic constriction injury of distal infraorbital nerve (IoN-CCI), was constructed and animal behaviors postsurgery were observed and analyzed. Trigeminal ganglia were collected for RNA-seq transcriptomics analysis. StringTie was used to annotate and quantify genome expression. DESeq2 was applied to compare between groups with P value less than 0.05 and fold change greater than 2 times and less than 0.5 times to screen differential genes, and display them with volcano graphs and cluster graphs. ClusterProfiler software was used to perform GO function enrichment analysis of differential genes. RESULTS: On the fifth postoperative day (POD5), the rat's face-grooming behavior increased to a peak; on the seventh postoperative day (POD7), the von-frey value dropped to the lowest value, indicating that the mechanical pain threshold of rats was significantly decreased. RNA-seq analysis of IoN-CCI rat ganglia found that the significantly up-regulated signaling pathways included B cell receptor signaling pathway, cell adhesion, complement and coagulation cascade pathways; significantly down-regulated pathways were related to systemic lupus erythematosus. Multiple genes among Cacna1s, Cox8b, My1, Ckm, Mylpf, Myoz1, Tnnc2 were involved in mediating the occurrence of trigeminal neuralgia. CONCLUSIONS: B cell receptor signaling pathway, cell adhesion, complement and coagulation cascade pathways, neuroimmune pathways are closely related to the occurrence of trigeminal neuralgia. The interaction of multiple genes among Cacna1s, Cox8b, My11, Ckm, Mylpf, Myoz1, Tnnc2 leads to the occurrence of trigeminal neuralgia.

Key words: Trigeminal neuralgia, RNA-Seq, Neuropathic pain

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