解剖学报 ›› 2021, Vol. 52 ›› Issue (3): 352-357.doi: 10.16098/j.issn.0529-1356.2021.03.004

• 神经生物学 • 上一篇    下一篇

海马小胶质细胞在小鼠慢性炎性痛所致负性情绪中的形态变化

李威刘志文曾佳玉曾学晴袁婧钟小林3* 万炜1,4*   

  1. 1.南华大学衡阳医学院应用解剖学与生殖医学研究所,湖南 衡阳 421001; 2.南华大学附属第二医院麻醉科,湖南 衡阳 421001; 3.南华大学附属第一医院内分泌疾病与代谢研究所,湖南 衡阳 421001; 4.海南医学院热带脑科学研究与转化重点实验室,海口 571199
  • 收稿日期:2020-10-22 修回日期:2021-01-28 出版日期:2021-06-06 发布日期:2021-06-06
  • 通讯作者: 钟小林;万炜 E-mail:david-wan@163.com
  • 基金资助:
    湖南省自然科学基金省市联合项目;湖南省自然科学基金青年项目;湖南省教育厅优秀青年项目;南华大学大学生研究性学习和创新性实验计划项目

Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia

LI Wei1  LIU Zhi-wen ZENG Jia-yu1  ZENG Xu-qing YUAN Jing1  ZHONG Xiao-lin3*  WAN Wei1,4*   

  1. 1.Clinical Anatomy and Reproductive Medicine Application Institute, School of Medicine, University of South China, Hu’nan Hengyang 421001, China; 2.Institute of Clinical Anesthesiology, the Second Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China;  3.Institute of Endocrine and Metabolic Diseases, the First Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China; 4.Key Laboratory of Brain Science Research and Transformation in Tropical Erivironment of Hainan Province, Haina Medical University, Haikou 571199, China
  • Received:2020-10-22 Revised:2021-01-28 Online:2021-06-06 Published:2021-06-06
  • Contact: ZHONG Xiao-lin;WAN Wei E-mail:david-wan@163.com

摘要:

目的  探讨完全弗氏佐剂(CFA)所致慢性炎性痛小鼠模型情绪及海马小胶质细胞形态的改变。   方法  32只ICR雄性小鼠随机分成生理盐水对照组(NS)和完全弗氏佐剂组(CFA)。右后爪足底注射CFA建立小鼠慢性炎性痛模型。采用Von Frey纤维针测量小鼠右足底注射CFA后机械痛阈的变化;采用旷场实验检测小鼠活动度和焦虑样行为;采用糖水偏好和被迫游泳实验检测小鼠抑郁样行为;采用免疫组织化学法检测小鼠海马小胶质细胞标记物离子钙接头蛋白抗原(IBA-1)的表达;采用Sholl分析方法分析海马齿状回区小胶质细胞形态变化。   结果  小鼠痛阈评分结果显示,与NS组相比,CFA组小鼠机械痛阈明显下降(P<0.05)。行为学结果显示,与NS组相比,CFA组小鼠旷场中央格停留时间减少(P<0.01),糖水偏好百分比下降(P<0.01),被迫游泳实验不动时间增加(P<0.001)。免疫组织化学结果显示,与NS组相比,CFA组小鼠海马齿状回区小胶质细胞数目明显增多(P<0.001)。Sholl分析结果显示,与NS组相比,CFA组小鼠海马齿状回区小胶质细胞交点数目减少(P<0.05)。   结论  在CFA诱导的慢性炎性痛模型中,小鼠的负性情绪可能与海马小胶质细胞形态改变有关。

关键词: 完全弗氏佐剂, 海马, 小胶质细胞, 慢性炎性痛, 负性情绪, 免疫组织化学, 小鼠

Abstract:

Objective  To investigate the alteration of mood and hippocampal microglia morphology in a mouse model of chronic inflammatory pain induced by complete Freund’s adjuvant (CFA).    Methods  Thirty-two male ICR mice were randomly divided into two groups, including normal saline control group (NS) and CFA model group (CFA). The pain model was established by right hindpaw intraplantar CFA injection. The change of mechanical pain threshold after CFA injection was measured by von Frey fiber needle, the locomotor activity and anxiety-like behavior were determined by open field test (OFT), the depression-like behavior was determined by sucrose preference test (SPT) and forced swimming test (FST). The expression of microglia marker ionized calcium binding adaptor molecule-1 (IBA-1) in the hippocampus was determined by immunohistochemistry and its morphological change was analyzed by Sholl analysis.   Results  Compared with the NS group, the mechanical pain threshold of CFA group decreased significantly (P<0.01). The behavior result  showed that the CFA group showed remarkably reduced time in the inner area (P<0.01) compared with the NS group in the open field test;In the sucrose preference test, the percentage of sucrose preference (P<0.01) of CFA mice decreased significantly compared with the NS mice, while the immobility time of CFA mice (P<0.01) increased significantly in the forced swimming test compared with the NS mice. The immunohistochemistry showed that the number of microglia in the dentate gyrus (DG) of CFA mice increased significantly compared with the NS mice. The Sholl analysis result  showed that compared with the NS mice, the number of intersections of microglia in hippocampal DG decreased significantly in CFA mice.   Conclusion  Our finding  indicates that the negative emotions in CFA-induced chronic inflammatory pain may be related to the morphological changes of hippocampal microglia in the mice.

Key words: Complete Freund’s adjuvant, Hippocampus, Microglia, Chronic inflammatory pain, Negative emotion, Immunohistochemistry, Mouse

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