Effect of <italic style="font-style: italic">Tongdu Tiaoshen</italic> acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway

ZHAO Yuxiao; GE Lei; ZHANG Bingjie; HE Yunyun; GE Lisheng

doi:10.13703/j.0255-2930.20250521-k0001

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Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway

Study on Mechanism | 更新时间：2026-03-16

- Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway
- Chinese Acupuncture & Moxibustion Vol. 46, Issue 3, Pages: 384-392(2026)
- 作者机构：
  
  张家口市第一医院康复医学科，河北张家口　075000
  河北北方学院附属第一医院康复医学科
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20250521-k0001
  CLC：
- Received：21 May 2025，
  
  Online First：24 November 2025，
  
  Published：12 March 2026
- 稿件说明：
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ZHAO Yuxiao, GE Lei, ZHANG Bingjie, et al. Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway[J]. Chinese Acupuncture & Moxibustion, 2026, 46(3): 384-392. DOI: 10.13703/j.0255-2930.20250521-k0001.
DOI：

ZHAO Yuxiao, GE Lei, ZHANG Bingjie, et al. Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway[J]. Chinese Acupuncture & Moxibustion, 2026, 46(3): 384-392. DOI: 10.13703/j.0255-2930.20250521-k0001. DOI：

摘要

目的：

基于趋化因子配体2-趋化因子受体2（CCL2-CCR2）通路探讨通督调神针刺对脑卒中后抑郁（PSD）大鼠海马神经元突触重塑的影响。

方法：

从62只雄性SD大鼠中随机选取50只采用大脑中动脉栓塞（MCAO）及慢性不可预知性温和应激（CUMS）法构建PSD模型，并将造模成功的48只大鼠随机分为模型组、针刺组、氟西汀组、针刺+激活剂组，每组12只，剩余12只正常大鼠作为空白组。针刺组采用通督调神针刺干预，穴取“大椎”“水沟”“神庭”“百会”，每次40 min，每日1次，每周6次；氟西汀组予5 mg/kg氟西汀灌胃，每日1次，每周7次；针刺+激活剂组予针刺+腹腔注射1 μg CCL2重组蛋白（rCCL2），腹腔注射每日1次，每周7次。对大鼠进行Longa评分、糖水偏好测试、强迫游泳测试；ELISA法检测大鼠血清炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）]含量；HE和Nissl染色法观察大鼠海马组织形态；透射电镜观察大鼠海马神经元突触超微结构；Western blot法检测大鼠海马CCL2-CCR2通路及神经元突触重塑相关蛋白表达。

结果：

与空白组比较，模型组海马组织形态结构损伤严重，神经元数目减少；突触数量减少、突触后致密带密度降低；Longa评分、游泳不动时间、TNF-α含量、IL-6含量及CCL2、CCR2蛋白表达增加（

0.05），糖水偏好指数、IL-10含量、突触体密度（SD）、突触后致密物厚度（PSDL）及突触蛋白1（SYN1）、突触囊泡素（SYN）、突触后密度蛋白95（PSD95）蛋白表达降低（

0.05）。与模型组比较，针刺组、氟西汀组海马组织形态结构损伤改善，尼氏小体增多；神经元核膜清晰，突触数量增多且相对密集、突触后致密带密度增加；Longa评分、游泳不动时间、TNF-α含量、IL-6含量及CCL2、CCR2蛋白表达降低（

0.05），糖水偏好指数、IL-10含量、SD、PSDL及SYN1、SYN、PSD95蛋白表达升高（

0.05）。与针刺+激活剂组比较，针刺组以上指标均改善（

0.05）。

结论：

通督调神针刺可改善PSD大鼠神经功能及抑郁样行为，可能通过抑制CCL2-CCR2通路改善海马神经元突触重塑实现。

Abstract

Objective

To investigate the effect of

Tongdu Tiaoshen

acupunc

ture (for unblocking the obstruction in the governor vessel and reulating the spirit) on hippocampal neuronal synaptic remodeling in rats with post-stroke depression (PSD) based on the chemokine ligand 2-chemokine receptor 2 (CCL2-CCR2) pathway.

Methods

Fifty male SD rats were randomly selected from a total of 62 rats to establish PSD model via middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Forty-eight successfully modeled rats were randomly divided into a model group

an acupuncture group

a fluoxetine group

and an acupuncture+agonist group

with 12 rats in each group. The remaining 12 normal rats were used as the blank group. The acupuncture group received

Tongdu Tiaoshen

acupuncture at "Dazhui" (GV14)

"Shuigou" (GV26)

"Shenting" (GV24)

and "Baihui" (GV20)

40 min per session

once daily

6 times per week. The fluoxetine group was administered with fluoxetine (5 mg/kg) by gavage once daily

7 times per week. The acupuncture+agonist group received acupuncture combined with intraperitoneal injection of recombinant CCL2 protein (1 μg)

once daily

7 times per week. Behavioral assessments included Longa neurological deficit score

sucrose preference test

and forced swimming test. ELISA was used to detect serum levels of inflammatory cytokines (tumor necrosis factor-α [TNF-α

]

interleukin-10 [IL-10

]

interleukin-6 [IL-6

]

). HE and Nissl staining were performed to observe hippocampal morphology. Transmission electron microscopy was used to observe the hippocampal synaptic ultrastructure. Western blot was used to detect the expression of CCL2-CCR2 pathway-related and neuronal synaptic remodeling-related proteins.

Results

Compared with the blank group

the model group exhibited severe damage to hippocampal structure

reduced neuronal number

decreased synapse count and postsynaptic density

increased Longa score

immobility time in the forced swimming test

TNF-α and IL-6 levels

and eleva

ted expression of CCL2 and CCR2 proteins (

0.05); while the sucrose preference index

IL-10 level

synaptic density (SD)

postsynaptic density thickness (PSDL)

and expression of synapsin 1 (SYN1)

synaptophysin (SYN)

and postsynaptic density proitein 95 (PSD95) proteins were significantly decreased (

0.05). Compared with the model group

both the acupuncture group and the fluoxetine group showed improved hippocampal structure

increased Nissl bodies

clearer neuronal nuclear membranes

increased synapse number and density

reduced Longa score

immobility time of swimming

TNF-αand IL-6 levels

and CCL2

CCR2 protein expression (

0.05)

and increased sucrose preference index

IL-10 level

PSDL

and SYN1

SYN

PSD95 protein expression (

0.05). Compared with the acupuncture+agonist group

the acupuncture group showed better improvement in all indexes (

0.05).

Conclusion

Tongdu Tiaoshen

acupuncture could improve neurological function and depressive-like behavior in PSD rats

possibly by inhibiting the CCL2-CCR2 pathway and promoting neuronal synaptic remodeling in the hippocampus.

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Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal synaptic remodeling in rats with post-stroke depression based on the CCL2-CCR2 pathway

DOI：10.13703/j.0255-2930.20250521-k0001

摘要

Abstract

关键词

Keywords

references