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

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。

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

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.