Zhongguo quanke yixue (Feb 2024)
Effect of Electroacupuncture on Inflammation Response and Ferroptosis in Rats Modeling Postoperative Cognitive Dysfunction
Abstract
Background Postoperative cognitive dysfunction (POCD) is one of the major causes of increased postoperative morbidity and mortality in patients. The inflammatory response and ferroptosis are the principal hypotheses of the mechanism of POCD development. But the mechanism of electroacupuncture to improve learning and memory function in POCD patients is unclear. Objective To observe the effect of electroacupuncture on learning, memory, inflammatory cytokines and ferroptosis of hippocampal neurons in aged rats with POCD, so as to explore the mechanism of improving POCD by electroacupuncture. Methods From January 2022 to February 2023, 72 SD rats aged 18 to 20 months were selected and divided into 3 groups according to random number table method of control group (n=24) , model group (n=24) and electroacupuncture group (n=24) . According to the observation time points of 3 and 7 days postoperative, the rats in each group were divided into 2 the subgroups (3 d postoperative subgroup in control group, 7 d postoperative subgroup in control group, 3 d postoperative subgroup in model group, 7 d postoperative subgroup in model group, 3 d postoperative subgroup in electroacupuncture group, 7 d postoperative subgroup in electroacupuncture group) , with 12 rats in each group. POCD model was established by exploratory laparotomy, and Baihui and Neiguan points were stimulated by electroacupuncture. The Morris water maze device was used to detect the behavioral performance of rats. The contents of interleukin (IL) 6, IL-10, tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected by enzyme-linked immunosorbent assay, and lipid peroxides (LPO) and Fe2+ in hippocampus were detected. The protein expression levels of acyl coenzyme A synthetase long-chain family member 4 (ACSL4) , ferritin heavy chain 1 (FTH1) and lysophosphatidylcholine acyltransferase-3 (LPCAT3) in hippocampus were detected by Western Blotting. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. Results Group and time had no interaction effect on the escape latency of cognitive function training at 3 and 7 d postoperatively (Pinteraction>0.05) , the main effect of training time on the escape latency of cognitive function training was significant (Ptime<0.05) , and the main effect of group on the escape latency was not significant (Pgroup>0.05) . The escape latency of 3 d postoperative subgroup in model group was higher than that of 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group. The frequency of crossing platform and target quadrant residence time of 3 d postoperative subgroup in model group were lower than those of 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group; the frequency of crossing platform in 3 d postoperative subgroup in electroacupuncture group was lower than that of 3 d postoperative subgroup in control group (P<0.05) . The escape latency of 7 d postoperative subgroup in model group was higher than that of 7 d postoperative subgroup in control group and 7 d postoperative subgroup in electroacupuncture group, the frequency of crossing platform was lower than that of 7 d postoperative subgroup in control group, and the target quadrant residence time was lower than that of 7 d postoperative subgroup in control group and 7 d postoperative subgroup in electroacupuncture group (P<0.05) . Serum IL-6 and TNF-α in 3 d postoperative subgroup in model group were higher than those in 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group (P<0.05) . TNF-α in 3 d postoperative subgroup in electroacupuncture group was higher than that in 3 d postoperative subgroup in control group (P<0.05) , and IL-10 was higher than that in 3 d postoperative subgroup in control group and 3 d postoperative subgroup in model group (P<0.05) . Serum IL-6 was higher in 7 d postoperative subgroup in model group than in 7 d postoperative subgroup in control group, and TNF-α was higher than 7 d postoperative subgroup in control group and 7 d postoperatively subgroup in electroacupuncture group, and IL-10 was higher in 7 d postoperative subgroup in electroacupuncture group than the 7 d postoperative subgroup in control group and 7 d postoperatively subgroup in model group (P<0.05) . The levels of hippocampal IL-6 and TNF-α in 3 d postoperative subgroup in model group were higher than those of 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group, and the level of IL-10 was higher than that of 3 d postoperative subgroup in control group and 3 d postoperative subgroup in model group (P<0.05) . Hippocampal IL-6 and TNF-α levels in 7 d postoperative subgroup in model group were higher than those in 7 d postoperative subgroup in control group and 7 d postoperative subgroup in electroacupuncture group, and IL-10 in 7 d postoperative subgroup in electroacupuncture group was higher than that in 7 d postoperative subgroup in contol group and 7 d postoperative subgroup in model group (P<0.05) . Fe2+, LPO, ACSL4 and LPCAT3 in 3 d postoperative subgroup in model group were higher than those in 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group, Fe2+, LPO, ACSL4 and LPCAT3 in 3 d postoperative subgroup in electroacupuncture group were higher than those in 3 d postoperative subgroup in control group; FTH1 in 3 d postoperative subgroup in model group was lower than that in 3 d postoperative subgroup in control group and 3 d postoperative subgroup in electroacupuncture group, FTH1 in 3 d postoperative subgroup in electroacupuncture group was lower than that in 3 d postoperative subgroup in control group (P<0.05) . Fe2+, LPO, ACSL4 and LPCAT3 in 7 d postoperative subgroup in model group were higher than those in 7 d postoperative subgroup in control group and 7 d postoperative subgroup in electroacupuncture group, FTH1 in 7 d postoperative subgroup in model group was lower than that in 7 d postoperative subgroup in control group and 7 d postoperative subgroup in electroacupuncture group (P<0.05) . In 3 d and 7 d postoperative subgroups in model group, the structure of double nuclear membrane of cell nucleus was clear in the hippocampal field of vision, and the perinuclear space was not significantly widened, with irregular shape and uneven surface; the chromatin in the nucleus was concentrated and marginalized; a small amount of mitochondrial membranes in the cytoplasm were broken and the membrane structure disappeared; part of the endoplasmic reticulum expanded obviously; some myelin sheaths were broken and disorganized. The 3 d and 7 d postoperative subgroups in electroacupuncture group improved significantly compared with 3 d and 7 d postoperative subgroups in model group. Conclusion The imbalance of inflammatory cytokines and ferroptosis of neurons may be the important etiological mechanism for the development of POCD. Electroacupuncture can improve the learning and memory abilities in aged rats with POCD, and the mechanism of its brain protection may be related to the regulation of systemic and central inflammatory cytokines and the pathway of ferroptosis in neurons.
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