实用医学杂志 ›› 2021, Vol. 37 ›› Issue (22): 2845-2850.doi: 10.3969/j.issn.1006⁃5725.2021.22.004

• 基础研究 • 上一篇    下一篇

脊髓背角神经元STAT3/SDF⁃1信号通路在大鼠术后慢性疼痛形成中的作用

孙扬1 张璎1 张海良2 李静3 孙文艳4   

  1. 西安医学院第二附属医院1 康复医学科,2 医务处,3 院办,4 耳鼻喉科(西安 710038)

  • 出版日期:2021-11-25 发布日期:2021-11-25
  • 通讯作者: 孙文艳 E⁃mail:19995561@qq.com
  • 基金资助:
    陕西省科技厅自然科学基础研究计划项目(编号:2018JM7052);陕西省教育厅专项科研计划项目(编号:18JK0675)

Mechanism of spinal dorsal horn SDF ⁃ 1 signaling pathway involved in chronic postsurgical pain

SUN Yang*,ZHANG Ying,ZHANG Hailiang,LI Jing,SUN Wenyan.    

  1. Department of Rehabilitation Medicine,the Sec⁃ ond Affiliated Hospital of Xi′an Medical University,Xi′an 710038,China 

  • Online:2021-11-25 Published:2021-11-25
  • Contact: SUN Wenyan E⁃mail:19995561@qq.com

摘要:

目的 本文旨在探讨脊髓背角神经元信号转导和转录激活因子 3(STAT3)/基质细胞衍生因 1(SDF⁃1)信号通路在大鼠形成术后慢性疼痛中的作用与机制。方法 建立大鼠皮肤肌肉切口牵拉 SMIR)术后慢性疼痛模型,鞘内用或不用 SDF⁃1 中和性抗体 antiSDF⁃1 STAT3 抑制剂 S3I⁃201,观察术前 及术后不同时点手术同侧机械性撤足阈值,脊髓背角 SDF⁃1 和转录激活因子 3(STAT3)表达水平及细胞 定位。另外,染色质免疫共沉淀(ChIP)检测 STAT3 SDF⁃1 启动子的相互作用。结果 与术前相比,术后 5、10、20 天大鼠机械性撤足反射阈值显著降低,伴有脊髓背角神经元 SDF⁃1 p⁃STAT3 表达上调,且均 Neun 阳性神经元共染。antiSDF⁃1 S3I⁃201 预处理均可缓解 SMIR 术后机械性撤足阈值改变,S3I⁃201 还降低术后SDF⁃1转录和翻译的上调。SMIR术后增加脊髓背角STAT3与SDF⁃1启动子结合。结论 SMIR 可能通过增强脊髓背角 STAT3 SDF⁃1 基因启动子的募集,上调SDF⁃1的表达,从而促进了机械性痛觉过 敏的发生发展。

关键词:

皮肤肌肉切口牵拉, 基质细胞衍生因子 1, 信号转导和转录激活因子 3, 术后慢性疼痛

Abstract:

Objective To investigate the effect and mechanism of STAT3/SDF⁃1 signaling pathway of spinal dorsal horn neurons in postoperative chronic pain. Methods A SMIR animal model,with or without antiSDF ⁃1 and S3I⁃201 intrathecally,was established. Mechanical withdrawal threshold on the ipsilateral side before and after operation,expression level of SDF⁃1 and STAT3,and cell location in the spinal dorsal horn were observed. In addition,ChIP was used to detect the interaction between STAT3 and SDF⁃1 promoter. Results The mechanical withdrawal threshold of rats on the 5th,10th,and 20th day after operation was significantly reduced,accompanied by up⁃regulation of the expression of SDF⁃1 and p⁃STAT3 in the spinal dorsal horn neurons,and all co⁃stained with Neun⁃positive neurons. AntiSDF⁃1 and S3I⁃201 pretreatment alleviated the changes in the mechanical withdrawal threshold after SMIR,and S3I ⁃201 also reduced the upregulation of SDF ⁃1 transcription and translation after surgery. After SMIR,the combination of STAT3 and SDF⁃1 promoter in the dorsal horn of the spinal cord was in⁃ creased. Conclusions STAT3/SDF⁃1 signaling pathway of spinal dorsal horn neurons is involved in the formation of postsurgical chronic pain.

Key words:

skin/muscle incision and retraction, stromal cell ?derived factor 1, signal transducer and activator of transcription 3, postoperative pain