Objective: The aim of this study was to investigate the role of ferroptosis in the occurrence of postoperative cognitive dysfunction (POCD) using a mouse model and to elucidate whether electroacupuncture (EA) can improve POCD by suppressing ferroptosis via the transferrin receptor 1 (TFR1)-divalent metal transporter 1 (DMT1)-ferroportin (FPN) pathway.
Methods: The experiment involved three groups: the control group, the POCD group and the POCD + EA group. The POCD animal model was established using sevoflurane anesthesia and tibial fracture. Cognitive and behavioral changes in mice were assessed using the novel object recognition test (NORT) and the Morris water maze (MWM) test, 1 and 3 days after surgery. Transmission electron microscopy was performed to observe changes in the mitochondrial structure of hippocampal tissue. Enzyme-linked immunosorbent assay was conducted to determine the levels of glutathione (GSH) and iron ion (Fe) concentrations. Western blot analysis was used to measure the expression of TFR1, DMT1 and iron pump protein. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to detect the mRNA levels of DMT1 and FPN.
Results: Based on the experimental results of the MWM test and the NORT, we found that EA can improve POCD in mice. Observation by projection electron microscopy showed that EA improved the mitochondrial structure in the hippocampus. The enzyme-linked immunosorbent assay (ELISA) results showed that EA suppressed ferroptosis in the hippocampal area. The qRT-PCR and Western blot results suggested that EA suppresses ferroptosis by regulating the TFR1-DMT1-FPN pathway.
Conclusion: This study reveals that sevoflurane and tibial fractures cause cognitive damage through the mechanism of ferroptosis, while EA may inhibit ferroptosis through the TFR1-DMT1-FPN pathway and improve POCD when induced in this way.
Keywords: eletroacupuncture; ferroptosis; postoperative cognitive dysfunction; tibial fractures.