南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (4): 899-906.doi: 10.12122/j.issn.1673-4254.2026.04.18
• • 上一篇
陈潇煜1(
), 刘畅1, 杨绍杰1, 王娟2, 程平2, 尹红宇1, 王婧吉1(
), 朱国旗2(
)
收稿日期:2025-06-06
出版日期:2026-04-20
发布日期:2026-04-24
通讯作者:
王婧吉,朱国旗
E-mail:cxy199906@163.com;wangjingji@ahtcm.edu.cn;Guoqizhu@gmail.com
作者简介:陈潇煜,在读硕士研究生,E-mail: cxy199906@163.com
基金资助:
Xiaoyu CHEN1(
), Chang LIU1, Shaojie YANG1, Juan WANG2, Ping CHENG2, Hongyu YIN1, Jingji WANG1(
), Guoqi ZHU2(
)
Received:2025-06-06
Online:2026-04-20
Published:2026-04-24
Contact:
Jingji WANG, Guoqi ZHU
E-mail:cxy199906@163.com;wangjingji@ahtcm.edu.cn;Guoqizhu@gmail.com
Supported by:摘要:
目的 探究电针对单次长时间应激(SPS)小鼠恐惧记忆消退的影响及星形胶质细胞(AST)参与的潜在机制。 方法 将36只雄性C57BL/6J小鼠随机分为6组(6只/组):实验一分为对照组、模型(SPS)组、电针治疗(EA)组和帕罗西汀阳性药(PRX)组;实验二分为Saline组和CNO组,通过化学遗传病毒抑制小鼠海马AST。除对照组外,其余各组采用SPS法进行模型制备。造模7 d后,EA、Saline和CNO组取“百会”“足三里”进行电针干预,PRX组予帕罗西汀溶液灌胃,连续干预10 d。采用条件性恐惧实验和高架十字迷宫实验评价小鼠恐惧记忆消退和焦虑样行为,其中CNO组在检测开始前30 min予CNO腹腔注射;采用Western blotting检测小鼠海马GFAP和CX43的蛋白表达。 结果 与对照组比较,SPS组小鼠恐惧再暴露阶段3~15 min内的凝滞时间、消退测试阶段的凝滞时间增加(P<0.05),恐惧消退指数、进入开放臂的时间降低(P<0.01),GFAP的平均荧光强度和AST的分支数量在距离胞体40~60 μm降低(P<0.05),海马GFAP和CX43蛋白的表达降低(P<0.05)。与SPS组比较,EA组与PRX组小鼠恐惧再暴露阶段3~6 min内的凝滞时间、消退测试阶段的凝滞时间降低(P<0.05),恐惧消退指数、进入开放臂的时间增加(P<0.05),GFAP的平均荧光强度增加(P<0.001),海马CX43蛋白的表达增加(P<0.05);EA组海马AST的分支数量在距离胞体50 μm增加(P<0.05)。与Saline组比较,CNO组小鼠恐惧再暴露阶段3~9 min内和消退测试阶段的凝滞时间增加(P<0.05),恐惧消退指数和进入开放臂的时间降低(P<0.05)。 结论 电针“百会”“足三里”可通过激活海马AST改善SPS小鼠的恐惧记忆消退障碍和焦虑样行为。
陈潇煜, 刘畅, 杨绍杰, 王娟, 程平, 尹红宇, 王婧吉, 朱国旗. 电针“百会”“足三里”通过激活海马星形胶质细胞改善单次长时间应激小鼠恐惧记忆消退障碍[J]. 南方医科大学学报, 2026, 46(4): 899-906.
Xiaoyu CHEN, Chang LIU, Shaojie YANG, Juan WANG, Ping CHENG, Hongyu YIN, Jingji WANG, Guoqi ZHU. Electroacupuncture at Baihui and Zusanli improves fear memory extinction in single prolonged stress mice by activating hippocampal astrocytes[J]. Journal of Southern Medical University, 2026, 46(4): 899-906.
图2 电针能改善SPS小鼠的恐惧记忆消退障碍和焦虑样行为
Fig.2 EA alleviates abnormal fear memory extinction and anxiety-like behaviors in SPS mice (n=6). A: Freezing time of mice during the re-exposure phase. B: Freezing time of mice during the fear extinction phase. C: Extinction coefficient of mice in FCT. D: Time in open arms of mice. *P<0.05, **P<0.01, ***P<0.001 vs CON group; #P<0.05, ##P<0.01, ###P<0.001 vs SPS group. SPS: Single prolonged stress. EA: Electroacupuncture. PRX: Paroxetine positive drug.
图3 电针能修复SPS小鼠海马GFAP下调和AST结构损伤
Fig.3 EA restores the down-regulation of GFAP and the structural damage of AST in the hippocampus of SPS mice (n=3). A: Immunofluorescence staining of GFAP (Nucleus: blue; AST: red; original magnification: ×200) and mean fluorescence intensity of GFAP in the hippocampus of the mice. B: Representative diagram and results of Sholl analysis. *P<0.05, ***P<0.001 vs CON group; #P<0.05, ###P<0.001 vs SPS group.
图4 电针能回调SPS小鼠海马GFAP和CX43蛋白的表达
Fig.4 EA restores the expression of GFAP and CX43 proteins in the hippocampus of SPS mice (n=3). A: Protein bands of GFAP and CX43 in Western blotting. B: Quantitative analysis of GFAP and CX43 expression levels. *P<0.05 vs CON group; #P<0.05 vs SPS group.
图5 抑制海马CA1区AST能阻断电针对SPS小鼠恐惧记忆消退障碍和焦虑样行为的改善作用
Fig. 5 Inhibition of astrocytes in hippocampal CA1 region of SPS mice blocks ameliorating effects of EA on abnormal fear memory extinction and anxiety-like behavior of SPS mice (n=6). A: Immunofluorescence staining for verifying virus injection (Nucleus: blue; AST: green; Virus: red; ×100). B: Freezing time of the mice during the re-exposure phase. C: Freezing time of mice during the fear extinction phase. D: Extinction coefficient of mice in FCT. E: Time in the open arms of the mice. *P<0.05, **P<0.01 vs Saline group.
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