Effect of <italic style="font-style: italic">Tongdu Tiaoshen</italic> acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway

QIAN Tingting; ZOU Ling; GAO Zhi; WU Yu; ZHAO Yanbiao; LI Nan; LIU Hui; SUN Meixiang; SUN Peiyang

doi:10.13703/j.0255-2930.20240917-k0001

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Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway

Study on Mechanism | 更新时间：2025-08-14

- Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway
- Chinese Acupuncture & Moxibustion Vol. 45, Issue 8, Pages: 1120-1127(2025)
- 作者机构：
  
  安徽中医药大学第二附属医院脑病七科，合肥　230061
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20240917-k0001
  CLC：
- Received：17 September 2024，
  
  Online First：03 December 2024，
  
  Published：12 August 2025
- 稿件说明：
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QIAN Tingting, ZOU Ling, GAO Zhi, et al. Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway[J]. Chinese Acupuncture & Moxibustion, 2025, 45(8): 1120-1127. DOI: 10.13703/j.0255-2930.20240917-k0001.
DOI：

QIAN Tingting, ZOU Ling, GAO Zhi, et al. Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway[J]. Chinese Acupuncture & Moxibustion, 2025, 45(8): 1120-1127. DOI: 10.13703/j.0255-2930.20240917-k0001. DOI：

摘要

目的：

观察“通督调神”针刺对抑郁症模型大鼠抑郁样行为及溶质载体家族7成员11（SLC7A11）/谷胱甘肽过氧化物酶4（GPX4）信号通路介导的海马神经元铁死亡的影响，探讨其治疗抑郁症的作用机制。

方法：

从30只SPF级雄性SD大鼠中选取24只，采用随机数字表法将大鼠分为正常组（8只）、造模组（16只），造模组大鼠进行连续28 d的慢性不可预知性温和应激（CUMS）刺激，建立抑郁症大鼠模型。造模结束后，将造模成功的16只大鼠随机分成模型组、针刺组，各8只。针刺组予“通督调神”针刺，穴取“大椎”“水沟”“百会”“神庭”，每日1次，连续干预6 d，第7天休息，共干预4周。于造模前、造模后、干预后行蔗糖偏好实验及旷场实验对大鼠进行行为学检测；干预后，采用HE及尼氏染色法观察大鼠海马神经元形态，Western blot法检测大鼠海马GPX4、SLC7A11、铁蛋白（Ferritin）、酰基辅酶A合成酶长链家族4（ACSL4）蛋白表达，实时荧光定量PCR法检测大鼠海马GPX4、SLC7A11、Ferritin、ACSL4 mRNA表达，比色法测定大鼠海马铁含量。

结果：

造模后，模型组、针刺组大鼠蔗糖偏好率及旷场实验运动总距离、直立次数、水平穿越格数低于正常组（

0.01）；干预后，针刺组大鼠蔗糖偏好率及旷场实验运动总距离、直立次数、水平穿越格数高于模型组（

0.01，

0.05）。与正常组比较，模型组大鼠海马坏死细胞数量增多、尼氏小体数量减少；与模型组比较，针刺组大鼠海马神经元固缩、坏死数量减少，细胞排列更加整齐，且神经元结构较分明，基质致密，血管数量稍丰富，尼氏小体数量增多。与正常组比较，模型组海马GPX4、SLC7A11蛋白及mRNA相对表达量降低（

0.01），海马Ferritin、ACSL4蛋白及mRNA相对表达量升高（

0.01）；与模型组比较，针刺组海马GPX4、SLC7A11蛋白及mRNA相对表达量升高（

0.01，

0.05），海马Ferritin、ACSL4蛋白及mRNA相对表达量降低（

0.01）。与正常组比较，模型组大鼠海马铁含量增多（

0.01）；与模型组比较，针刺组大鼠海马铁含量减少（

0.05）。

结论：

“通督调神”针刺可改善抑郁症模型大鼠抑郁样行为，其机制可能与调节SLC7A11/GPX4信号通路、抑制海马神经元铁死亡相关。

Abstract

Objective

To observe the effects of

Tongdu Tiaoshen

acupuncture (acupuncture for unblocking the obstruction in the governor vessel and regulating the spirit) on the depression-like behavior and the hippocampal neuronal ferroptosis mediated by solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway in depression rats

and explore the mechanism of this therapy for depression.

Methods

Of 30 male SD rats of SPF grade

24 rats were selected. According to the random number table

they were divided into a normal group (

=8) and a modeling group (

=16). The rats in the modeling group were subjected to chronic unpredictable mild stress (CUMS) for 28 consecutive days to establish depression model. After modeling

16 successfully-modeled rats were randomly divided into a model group and an acupuncture group

8 rats in each one. In the acupuncture group

Tongdu Tiaoshen

acupuncture was applied to "Dazhui"(GV14)

"Shuigou" (GV26)

"Baihui" (GV20) and "Shenting" (GV24). This intervention measure was deliveredonce a day

continuously for 6 days. The intervention discontinued on day 7

and was completed in 4 weeks. Before and after modeling

and after intervention completion

the behavioristics detection was performed using sucrose preference experiment and open field experiment. After intervention

using hematoxylin-eosin (HE) and Nissl staining

the morphology of hippocampal neurons was observed; with Western blot method

the protein expression of GPX4

SLC7A11

Ferritin and acyl-CoA synthetase long-chain family 4 (ACSL4) in hippocampal tissues was detected; with the real-time fluorescence quantitative PCR adopted

the mRNA expression of GPX4

SLC7A11

Ferritin and ACSL4 was detected; and using colorimetry

the hippocampal iron content was determined.

Results

After modeling

the sucrose preference rates

the total distance of movement

the standing times and the boxes of horizontal crossing in the model group and the acupuncture group were lower than those in the normal group (

0.01). After the intervention

the sucrose preference rates

the total distance of movement

the standing times and the boxes of horizontal crossing in the acupuncture group were higher than those in the model group (

0.01

0.05). Compared with the normal group

the number of necrotic cells increased and the number of Nissl bodies decreased in the model group; and when compared with the model group

the neuronal pyknosis and necrosis were ameliorated

the cells were arranged more regularly

the neuronal structure was clear

the matrix was dense

the blood vessels were enriched and the number of Nissl bodies increased in the acupuncture group. In comparison with the normal group

the relative expression of protein and mRNA of hippocampal GPX4

SLC7A11 decreased (

0.01)

it increased in the expression of hippocampal Ferritin and ACSL4 (

0.01) in the model group. When compared with the model group

in the acupuncture group

the relative expression of protein and mRNA of hippocampal GPX4

SLC7A11 was elevated (

0.01

0.05)

it was dropped for hippocampal Ferritin and ACSL4 (

0.01). In the model group

the hippocampal iron content was elevated when compared with that in the normal group (

0.01); and it was reduced in the acupuncture group when compared with that in the model group (

0.05).

Conclusion

Tongdu Tiaoshen

acupuncture attenuates depression-like behaviors in the depression rats

which may be related to regulating SLC7A11/GPX4 pathway and inhibiting neuronal ferroptosis in the hippocampus.

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⁰

Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway

DOI：10.13703/j.0255-2930.20240917-k0001

摘要

Abstract

关键词

Keywords

references