Research Paper Volume 12, Issue 13 pp 13187—13205

Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway

Zhi-Gang Mei1,2, *, , Ya-Guang Huang3, *, , Zhi-Tao Feng2, , Ya-Nan Luo2, , Song-Bai Yang4, , Li-Peng Du2, , Kang Jiang2, , Xiao-Lu Liu2, , Xian-Yun Fu2, , Yi-Hui Deng1, , Hua-Jun Zhou5, ,

  • 1 Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan, China
  • 2 Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, China
  • 3 Affiliated Renhe Hospital of China Three Gorges University, Yichang, Hubei, China
  • 4 Yichang Hospital of Traditional Chinese Medicine, Clinical Medical College of Traditional Chinese Medicine, China Three Gorges University, Yichang, Hubei, China
  • 5 The Institute of Neurology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China
* Equal contribution

Received: January 8, 2020       Accepted: May 27, 2020       Published: July 3, 2020
How to Cite

Copyright © 2020 Mei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at “Baihui”, “Quchi” and “Zusanli” acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.


Ac-FOXO1: acetylated Forkhead box O1; Atg7: autophagy-related gene 7; CCA: common carotid artery; CIR: cerebral ischemia/reperfusion; DAPI: 4′,6-diamidino-2-phenylindole; EA: electroacupuncture; ECA: external carotid artery; FDA: the U.S. Food and Drug Administration; FOXO1: Forkhead box O1; ICA: internal carotid artery; I/R: ischemia/reperfusion; LC3: microtubule-associated protein 1 light chain 3; MCAO: middle cerebral artery occlusion; PBS: phosphate buffered saline; PVDF: polyvinylidene fluoride; r-tPA: recombinant tissue-plasminogen activator; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIRT1: Silent information regulator 1; TTC: 2,3,5-triphenyltetrazolium chloride.