Mechanism of electroacupuncture for attenuating duodenal injury in rats with functional dyspepsia via Keap1/Nrf2/GPX4 pathway-mediated ferroptosis

FENG Yifan; LIU Jidong; QU Yi; XUE Yanan; WANG Jianbo; LI Yang; WANG Tianlang; WANG Xihan; ZHANG Jiahao; LIANG Tingting; TIAN Yuelong; HAN Lei

doi:10.13703/j.0255-2930.20250624-k0004

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Mechanism of electroacupuncture for attenuating duodenal injury in rats with functional dyspepsia via Keap1/Nrf2/GPX4 pathway-mediated ferroptosis

Study on Mechanism | 更新时间：2026-04-16

- Mechanism of electroacupuncture for attenuating duodenal injury in rats with functional dyspepsia via Keap1/Nrf2/GPX4 pathway-mediated ferroptosis
- Chinese Acupuncture & Moxibustion Vol. 46, Issue 4, Pages: 580-588(2026)
- 作者机构：
  
  辽宁中医药大学，针灸推拿学院，沈阳　110847
  辽宁中医药大学，中医脏象理论及应用教育部重点实验室，沈阳　110847
  辽宁中医药大学，实验动物医学院，沈阳　110847
  辽宁中医药大学附属第二医院
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20250624-k0004
  CLC：
- Received：24 June 2025，
  
  Online First：02 February 2026，
  
  Published：12 April 2026
- 稿件说明：
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FENG Yifan, LIU Jidong, QU Yi, et al. Mechanism of electroacupuncture for attenuating duodenal injury in rats with functional dyspepsia via Keap1/Nrf2/GPX4 pathway-mediated ferroptosis[J]. Chinese Acupuncture & Moxibustion, 2026, 46(4): 580-588.
DOI：

FENG Yifan, LIU Jidong, QU Yi, et al. Mechanism of electroacupuncture for attenuating duodenal injury in rats with functional dyspepsia via Keap1/Nrf2/GPX4 pathway-mediated ferroptosis[J]. Chinese Acupuncture & Moxibustion, 2026, 46(4): 580-588. DOI： 10.13703/j.0255-2930.20250624-k0004.

摘要

目的：

基于Kelch样环氧氯丙烷相关蛋白1（Keap1）/核因子E2相关因子2（Nrf2）/谷胱甘肽过氧化物酶4（GPX4）通路介导铁死亡探讨电针“足三里”“太冲”调控功能性消化不良（FD）大鼠十二指肠损伤的机制。

方法：

将21只SPF级雄性SD大鼠随机分为正常组、模型组、电针组，每组7只。模型组、电针组大鼠采用轻度夹尾刺激＋间断饮食双因素复合法构建FD肝郁脾虚证模型。造模结束后，对电针组进行电针双侧“足三里”“太冲”干预，采用疏密波，频率2 Hz/100 Hz，每次20 min，每日1次，共干预14 d。观察大鼠一般状况；测定大鼠胃排空率及肠推进率；HE染色法观察大鼠十二指肠组织形态；免疫组化法检测大鼠十二指肠组织Keap1、Nrf2、GPX4阳性表达；免疫荧光法检测大鼠十二指肠组织活性氧（ROS）阳性表达；生化法检测大鼠十二指肠组织亚铁离子（Fe

）及血清丙二醛（MDA）、还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）含量；ELISA法检测大鼠血清三磷酸腺苷（ATP）含量；实时荧光定量PCR法检测大鼠十二指肠组织Keap1、Nrf2、GPX4 mRNA表达；Western blot法检测大鼠十二指肠组织Keap1、Nrf2、GPX4、酰基辅酶A合成酶长链家族4（ACSL4）、溶质载体家族7成员11（SLC7A11）蛋白表达。

结果：

与正常组比较，模型组大鼠饮食量、体质量、胃排空率、肠推进率降低（

0.05）；十二指肠黏膜层肠绒毛结构紊乱，出现炎症细胞浸润；ROS阳性表达及Fe

、MDA含量升高（

0.05）；GSH、SOD、ATP含量降低（

0.05）；Nrf2、GPX4 mRNA和Nrf2、GPX4、SLC7A11蛋白表达降低（

0.05），Keap1 mRNA和Keap1、ACSL4蛋白表达升高（

0.05）。与模型组比较，电针组大鼠饮食量、体质量、胃排空率、肠推进率升高（

0.05）；十二指肠黏膜结构基本完整，固有层无炎症细胞浸润；ROS阳性表达及Fe

、MDA含量降低（

0.05）；GSH、SOD、ATP含量升高（

0.05）；Nrf2、GPX4 mRNA和Nrf2、GPX4、SLC7A11蛋白表达升高（

0.05），Keap1 mRNA和Keap1、ACSL4蛋白表达降低（

0.05）。

结论：

电针“足三里”“太冲”可能通过调控Keap1/Nrf2/GPX4通路减轻FD大鼠十二指肠的脂质过氧化水平与氧化应激损伤，维持细胞内铁稳态，抑制铁死亡，进而改善FD。

Abstract

Objective

To investigate the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) and "Taichong" (LR3) for attenuating duodenal injury in rats with functional dyspepsia (FD) based on ferroptosis mediated by Kelch-like epichlorohydrin-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway.

Methods

A total of 21 SPF-grade SD male rats were randomly divided into a normal group

a model group and an EA group

7 rats in each one. In the model and EA groups

FD (liver stagnation and spleen deficiency) models were prepared by dual-factor combination method

using mild tail clamping

stimulation and intermittent diet. After model preparation

in the EA group

EA was operated at bilateral "Zusanli" (ST36) and "Taichong" (LR3)

with a disperse-dense wave

a frequency of 2 Hz/100 Hz and for 20 min each session

once a day

and the duration of intervention was composed of 14 days. The general condition of the rats was observed. The gastric emptying rate and intestinal propulsion rate were measured. The pathomorphologic changes of duodenal tissue were observed by HE staining method; the positive expression of Keap1

Nrf2 and GPX4 in duodenal tissue was detected using immunohistochemistry and the positive expression of reactive oxygen species (ROS) in duodenal tissue was detected using immunofluorescence. The levels of ferrous ions (Fe

) in duodenal tissue

and malondialdehyde (MDA)

reduced glutathione (GSH) and superoxide dismutase (SOD) in serum were detected using biochemical methods

ATP level in serum was detected using ELISA

and the mRNA expression of Keap1

Nrf2

and GPX4 in duodenal tissue was detected by real-time fluorescence quantitative PCR (RT-qPCR); and the protein expression of Keap1

Nrf2

GPX4

acyl-CoA synthase long-chain family 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) was detected using Western blot.

Results

Compared with the normal group

the rats in the model group exhibited the decrease in food intake

body weight

gastric emptying rate and intestinal propulsion rate (

0.05). In the duodenal tissue

the intestinal villi were disordered

and the inflammatory cells infiltrated. The positive expression of ROS

and the contents of Fe

and MDA were elevated (

0.05)

the levels of GSH

SOD and ATP decreased (

0.05)

the mRNA expression of Nrf2 and GPX4 and the protein expression of Nrf2

GPX4 and SLC7A11 were reduced (

0.05)

while the mRNA expression of Keap1 and the protein expression of Keap1 and ACSL4 were elevated (

0.05). When compared with the model group

the rats in the EA group showed the increase in food intake

body weight

gastric emptying rate and intestinal propulsion rate (

0.05). In the duodenal tissue

the structure of the intestinal mucosa was intact basically

without inflammatory cell infiltration in the lamina propria. The positive expression of ROS

and the contents of Fe

and MDA were dropped (

0.05)

the contents of GSH

SOD and ATP rose (

0.05)

the mRNA expression of Nrf2 and GPX4 and the protein expression of Nrf2

GPX4 and SLC7A11 were elevated (

0.05)

while the mRNA expression of Keap1 and the protein expression of Keap1 and ACSL4 were reduced (

0.05).

Conclusion

Electroacupuncture at "Zusanli" (ST36) and "Taichong" (LR3) alleviates lipid peroxidation and oxidative stress injury in the duodenum of FD rats

maintains intracellular iron homeostasis

and inhibits ferroptosis probably by regulating Keap1/Nrf2/GPX4 pathway

so as to attenuate FD.

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