[Effect of acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway].

OBJECTIVE

To observe the effects of acupuncture (acupuncture for unblocking the obstruction in the governor vessel and regulating the spirit) on the depression-like behavior and the hippocampal neuronal ferroptosis mediated by solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway in depression rats, and explore the mechanism of this therapy for depression.

METHODS

Of 30 male SD rats of SPF grade, 24 rats were selected. According to the random number table, they were divided into a normal group (=8) and a modeling group (=16). The rats in the modeling group were subjected to chronic unpredictable mild stress (CUMS) for 28 consecutive days to establish depression model. After modeling, 16 successfully-modeled rats were randomly divided into a model group and an acupuncture group, 8 rats in each one. In the acupuncture group, acupuncture was applied to "Dazhui"(GV14), "Shuigou" (GV26), "Baihui" (GV20) and "Shenting" (GV24). This intervention measure was deliveredonce a day, continuously for 6 days. The intervention discontinued on day 7, and was completed in 4 weeks. Before and after modeling, and after intervention completion, the behavioristics detection was performed using sucrose preference experiment and open field experiment. After intervention, using hematoxylin-eosin (HE) and Nissl staining, the morphology of hippocampal neurons was observed; with Western blot method, the protein expression of GPX4, SLC7A11, Ferritin and acyl-CoA synthetase long-chain family 4 (ACSL4) in hippocampal tissues was detected; with the real-time fluorescence quantitative PCR adopted, the mRNA expression of GPX4, SLC7A11, Ferritin and ACSL4 was detected; and using colorimetry, the hippocampal iron content was determined.

RESULTS

After modeling, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the model group and the acupuncture group were lower than those in the normal group (<0.01). After the intervention, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the acupuncture group were higher than those in the model group (<0.01, <0.05). Compared with the normal group, the number of necrotic cells increased and the number of Nissl bodies decreased in the model group; and when compared with the model group, the neuronal pyknosis and necrosis were ameliorated, the cells were arranged more regularly, the neuronal structure was clear, the matrix was dense, the blood vessels were enriched and the number of Nissl bodies increased in the acupuncture group. In comparison with the normal group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 decreased (<0.01), it increased in the expression of hippocampal Ferritin and ACSL4 (<0.01) in the model group. When compared with the model group, in the acupuncture group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 was elevated (<0.01, <0.05), it was dropped for hippocampal Ferritin and ACSL4 (<0.01). In the model group, the hippocampal iron content was elevated when compared with that in the normal group (<0.01); and it was reduced in the acupuncture group when compared with that in the model group (<0.05).

CONCLUSION

acupuncture attenuates depression-like behaviors in the depression rats, which may be related to regulating SLC7A11/GPX4 pathway and inhibiting neuronal ferroptosis in the hippocampus.