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- Title
Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke.
- Authors
Yang, Xi-chen; Jin, Ya-ju; Ning, Rong; Mao, Qiu-yue; Zhang, Peng-yue; Zhou, Li; Zhang, Cheng-cai; Peng, Yi-chen; Chen, Na
- Abstract
Objective: Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis has been shown to play a key role in the injury process. In the present study, we wanted to explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation. Methods: The ischemic stroke model was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in adult rats. These rats have been randomly divided into the EA MCAO/R group, the MCAO/R group, the EA MCAO/R Brusatol group (the inhibitor of Nrf2), and the EA MCAO/R DMSO group, and the Sham group. The EA MCAO/R group, EA MCAO/R Brusatol group, and the EA MCAO/R DMSO group received EA intervention 24 h after modeling for 7 consecutive days. The behavioral function was evaluated by Neurologic severity score (NSS), Garcia score, Foot-fault Test, and Rotarod Test. The infarct volume was detected by TTC staining, and the neuronal damage was observed by Nissl staining. The levels of Fe2 , reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by ELISA. The immunofluorescence and Western blotting were used to detect the expression of Total Nrf2, p-Nrf2, Nuclear Nrf2, and Cytoplasmic Nrf2, and the essential ferroptosis proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1). The mitochondria were observed by transmission electron microscopy (TEM). Results: Electroacupuncture improved neurological deficits in rats model of MCAO/R, decreased the brain infarct volume, alleviated neuronal damage, inhibited the Fe2 , ROS, and MDA accumulation, increased SOD levels, increased the expression of GPX4, SLC7A11 and FTH1, and rescued injured mitochondria. Especially, we found that the electroacupuncture up-regulated the expression of Nrf2, and promoted phosphorylation of Nrf2 and nuclear translocation, However, Nrf2 inhibitor Brusatol reversed the neuroprotective effect of electroacupuncture. Conclusion: Electroacupuncture can alleviate cerebral I/R injury-induced ferroptosis by promoting Nrf2 nuclear translocation. It is expected that these data will provide novel insights into the mechanisms of electroacupuncture protecting against cerebral I/R injury and potential targets underlying ferroptosis in the stroke.
- Subjects
SUPEROXIDE dismutase; MITOCHONDRIA; PHOSPHORYLATION; DATA analysis; RESEARCH funding; APOPTOSIS; ELECTRON microscopy; ENZYME-linked immunosorbent assay; CELLULAR signal transduction; FLUORESCENT antibody technique; OXIDATIVE stress; DESCRIPTIVE statistics; ELECTROACUPUNCTURE; RATS; REACTIVE oxygen species; ISCHEMIC stroke; ANIMAL experimentation; WESTERN immunoblotting; GENE expression profiling; ONE-way analysis of variance; STATISTICS; STAINS & staining (Microscopy); GLUTATHIONE peroxidase; CONFIDENCE intervals; DATA analysis software; NUCLEAR factor E2 related factor; MALONDIALDEHYDE
- Publication
Chinese Medicine, 2025, Vol 20, Issue 1, p1
- ISSN
1749-8546
- Publication type
Academic Journal
- DOI
10.1186/s13020-024-01047-0