Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with <italic style="font-style: italic">Shugan Tiaoshen</italic> acupuncture for alleviating chronic inflammatory pain and depression comorbidity

LIU Guanghua; FU Wen; WU Yisen; WANG Mengyu; GAO Jing; WU Lihua; WANG Zihua; SHI Dongliang

doi:10.13703/j.0255-2930.20241115-k0006

您当前的位置：

首页 >

文章列表页 >

Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity

Study on Mechanism | 更新时间：2026-01-16

- Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity
- Chinese Acupuncture & Moxibustion Vol. 46, Issue 1, Pages: 85-96(2026)
- 作者机构：
  
  河南中医药大学第一附属医院风湿病科，郑州　450000
  南京中医药大学附属南京中医院针灸科，江苏南京　210022
  河南中医药大学骨伤学院，郑州　450046
  湖北中医药大学针灸骨伤学院
  河南中医药大学康复医学院
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20241115-k0006
  CLC：
- Received：15 November 2024，
  
  Online First：18 March 2025，
  
  Published：12 January 2026
- 稿件说明：
移动端阅览
LIU Guanghua, FU Wen, WU Yisen, et al. Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity[J]. Chinese Acupuncture & Moxibustion, 2026, 46(1): 85-96. DOI: 10.13703/j.0255-2930.20241115-k0006.
DOI：

LIU Guanghua, FU Wen, WU Yisen, et al. Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity[J]. Chinese Acupuncture & Moxibustion, 2026, 46(1): 85-96. DOI: 10.13703/j.0255-2930.20241115-k0006. DOI：

摘要

目的：

观察“疏肝调神”针刺对慢性炎性痛与抑郁共病（CIPDC）大鼠海马神经元线粒体自噬和氧化应激相关因子的影响及对海马神经元的保护作用，探讨“疏肝调神”针刺改善CIPDC的可能机制。

方法：

从60只SD大鼠中随机取12只作为对照组，余大鼠采用左后足趾面皮下注射完全弗氏佐剂的方法构建CIPDC模型，将造模成功的48只大鼠分为模型组、电针组、抑制剂组、电针+抑制剂组，每组12只。电针组大鼠予电针干预，穴取“印堂”“百会”及双侧“合谷”“太冲”，合谷、太冲连接电针（同侧穴位为1组，选用疏密波、频率2 Hz /10 Hz、电流1 mA），每日30 min；抑制剂组大鼠予自噬抑制剂3-甲基腺嘌呤（3-MA）腹腔注射；电针+抑制剂组大鼠予腹腔注射3-MA后再予电针干预。均每日1次，持续14 d。采用机械刺激缩足反射阈值（PWMT）、热缩足反射潜伏期（PTWL）评价大鼠疼痛阈值；糖水偏好实验、旷场实验、强迫游泳评价大鼠抑郁样行为；HE染色观察大鼠海马神经元形态；Fluoro-Jade B染色观察大鼠海马神经元损伤变性情况；透射电镜观察大鼠海马神经元线粒体超微结构；流式细胞术检测大鼠海马组织活性氧（ROS）含量；比色法检测大鼠海马组织丙二醛（MDA）、超氧化物歧化酶（SOD）含量；Western blot法检测大鼠海马组织隔离体蛋白1（p62）、PTEN 诱导的假定激酶1（PINK1）、帕金蛋白（Parkin）、苄氯素1（Beclin1）、微管相关蛋白1A/1B轻链3（LC3）蛋白表达；实时荧光定量PCR法检测大鼠海马组织p62、PINK1、Parkin、Beclin1 mRNA表达。

结果：

与对照组比较，模型组大鼠PWMT、PTWL及蔗糖偏好率、运动总距离、中心区域运动时间降低（

0.05），漂浮时间升高（

0.05）；海马神经元排列松散，核膜破裂，变性神经元数量增加（

0.05）；线粒体破裂肿胀、内部嵴断裂或消失；ROS、MDA含量升高（

0.05），SOD含量降低（

0.05）；海马组织p62、PINK1、Parkin、Beclin1蛋白及mRNA表达和LC3蛋白表达差异无统计学意义（

0.05）。与模型组比较，电针组大鼠PWMT、PTWL及蔗糖偏好率、运动总距离、中心区域运动时间升高（

0.05），漂浮时间降低（

0.05）；海马神经元形态圆润，排列整齐，变性神经元数量减少（

0.0

5）；线粒体形态较为正常，双层膜结构较为完整，可见自噬小体出现；ROS、MDA含量降低（

0.05），SOD含量升高（

0.05）；海马组织p62蛋白及mRNA表达降低（

0.05），PINK1、Parkin、Beclin1蛋白及mRNA表达升高（

0.05），LC3蛋白表达升高（

0.05）。与电针组比较，电针+抑制剂组大鼠PWMT、PTWL及蔗糖偏好率、运动总距离、中心区域运动时间降低（

0.05），漂浮时间升高（

0.05）；海马神经元排列更紊乱，核膜损伤增加，变性神经元数量增加（

0.05）；线粒体双层膜及嵴损伤明显；ROS、MDA含量升高（

0.05），SOD含量降低（

0.05）；海马组织p62蛋白及mRNA表达升高（

0.05），PINK1、Parkin、Beclin1蛋白及mRNA表达降低（

0.05），LC3蛋白表达降低（

0.05）。

结论：

“疏肝调神”针刺可能通过调控PINK1/Parkin信号通路增强海马神经元线粒体自噬发挥对CIPDC大鼠的保护作用。

Abstract

Objective

To observe the effects of

Shugan Tiaoshen

acupuncture (acupuncture for smoothing liver

and regulating the mind) on hippocampal neural mitophagy and oxidative stress-related factors in the rats with chronic inflammatory pain and depression comorbidity (CIPDC)

and its protective effect on hippocampal neurons; and explore the underlying mechanism of this acupuncture therapy for alleviating CIPDC.

Methods

Of 60 Sprague-Dawley (SD) rats

12 rats were randomly selected as the control group. CIPDC models were established by subcutaneous injection with complete Freund's adjuvant (CFA) into the plantar region of the left hind paws of the rest rats. Forty-eight successfully modeled rats were assigned into a model group

an electroacupuncture (EA) group

an inhibitor group and an EA + inhibitor group

12 rats in each one. In the EA group

EA was applied to "Yintang" (GV24

)

"Baihui" (CV20)

and bilateral "Hegu" (LI4) and "Taichong" (LR3). Electric stimulation was delivered at "Hegu" (LI4) and "Taichong" (LR3) unilaterally

with disperse-dense wave

a frequency of 2 Hz/10 Hz

and a current of 1 mA. EA w

as operated for 30 min daily. In the inhibitor group

autophagy inhibitor

3-methl adenine (3-MA) was injected intraperitoneally. In the EA + inhibitor group

EA was delivered after intraperitoneal injection with 3-MA. The intervention of each group was operated once daily and for 14 consecutive days. Pain threshold was assessed using paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PTWL). Depressive-like behaviors were evaluated using the sucrose preference test

open-field test

and forced swimming test. Hematoxylin and eosin (HE) staining was used to observe the pathological morphology of hippocampal neurons. Fluoro-Jade B staining was performed to assess hippocampal neuronal injury and degeneration. Transmission electron microscopy (TEM) was employed to examine the ultrastructure of hippocampal mitochondria. Hippocampal reactive oxygen species (ROS) expression was detected using flow cytometry. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampus were measured using a colorimetric method. Western blot analysis was conducted to detect the protein expression of sequenstering protein 1 (p62)

PTEN induced putative kinase 1 (PINK1)

Parkin protein (Parkin)

Beclin1

and microtubule-associated protein 1A/1B 1ight chain3 (LC3) in the hippocampus. Real-time PCR was used to detect the mRNA expression of p62

PINK1

Parkin and Beclin1.

Results

Compared with the control group

in the model group

PWMT

PTWL

sucrose preference rate

total distance traveled in the open field

and time spent in the center area decreased (

0.05)

while the immobility time increased (

0.05); the mitochondria was ruptured and swollen and the internal crista were broken or disappeared; the content of ROS and MDA elevated (

0.05) and SOD reduced (

0.05); the protein and mRNA expression of hippocampal p62

PINK1

Parkin and Beclin 1

as well as the protein expression

of LC3 were not different statistically (

0.05). Compared with the model group

in the EA group

PWMT

PTWL

sucrose preference rate

total distance traveled in the open field

and time spent in the center area increased (

0.05)

while the immobility time decreased (

0.05); hippocampal neurons were rounded and neatly arranged

with the number of degenerated neurons declined (

0.05); the mitochondrial morphology was relatively normal

and the bilayer membrane structure intact

and autophagosomes visible; the content of ROS and MDA reduced (

0.05) and SOD elevated (

0.05); the protein and mRNA expression of hippocampal p62 was declined (

0.05)

and the protein and mRNA expression of PINK1

Parkin and Beclin 1 was elevated (

0.05)

and the protein expression of LC3 rose (

0.05). When compared with the EA group

in the EA + inhibitor group

PWMT

PTWL

sucrose preference rate

total distance traveled in the open field

and time spent in the center area were reduced (

0.05)

while the immobility time was higher (

0.05); hippocampal neurons were more disarranged

with increased nuclear membrane damage and more degenerated neurons (

0.05); the damage in mitochondrial bilayers and cristae was obvious; the content of ROS and MDA higher (

0.05) and SOD lower (

0.05); the protein and mRNA expression of hippocampal p62 was elevated (

0.05)

and protein and mRNA expression of PINK1

Parkin and Beclin 1 was reduced (

0.05)

and the protein expression of LC3 decreased (

0.05).

Conclusion

Shugan Tiaoshen

acupuncture presents a protective effect on CIPDC by enhancing hippocampal neuronal mitophagy through regulating the PINK1/Par

kin pathway in the model rats.

关键词

Keywords

references

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of eye acupuncture on mitophagy in neurons of ischemic cortical brain tissue in rats with cerebral ischemia reperfusion injury based on AMPK/ULK1/FUNDC1 signaling axis

Tongdu Jieyu acupuncture combined with local surrounding needling for 34 cases of melasma with liver qi stagnation

Effects of electroacupuncture on cognitive impairment and mitophagy mediated by KIF5A/Miro1 pathway in Parkinson's disease mice

Heat-sensitive moxibustion robot for improving depressive state in methamphetamine addicts during withdrawal period: a randomized controlled trial

Acupuncture and moxibustion combined with umbilical therapy for 30 cases of anxiety and depression in patients with neurogenic bladder after spinal cord injury

Related Author

CHU Haoran

WANG Zhen

CHENG Jingyan

PU Yanpeng

CHEN Guisheng

SUN Zizhi

GU Xiyan

TANG Mingjie

Related Institution

Famous Doctor Clinic, Second Affiliated Hospital of Anhui University of CM

Department of Rehabilitation, Second Affiliated Hospital of Anhui University of CM

Department of Encephalopathy, Second Affiliated Hospital of Anhui University of CM

Postdoctoral Research Station, Anhui University of CM

Nanjing Hospital of TCM Affiliated to Nanjing University of Chinese Medicine

⁰

Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity

DOI：10.13703/j.0255-2930.20241115-k0006

摘要

Abstract

关键词

Keywords

references