陆军军医大学学报 (Mar 2023)
Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis
Abstract
Objective To investigate the effect of hypoxia combined with propofol on immature Sprague-Dawley (SD) rat hippocampal neurons through ferroptosis. Methods A total of 168 7-day-old SD rats (half male and half female, 15.59±1.13 g) were randomly divided into 6 groups (n=28): lipid emulsion solvent+50% oxygen (CO), lipid emulsion solvent+air (CA), lipid emulsion solvent+18% oxygen (CH), propofol+50% oxygen (PO), propofol+air (PA), and propofol+18% oxygen (PH) groups.The rats in the propofol group were intraperitoneally injected with 50 mg/kg propofol, and those in the lipid emulsion group were intraperitoneally injected with 5 mL/kg lipid emulsion, once a day for 7 consecutive days.After injection, the mice were put into warm chambers with oxygen concentration of 50%, 21% and 18%(38℃) respectively.After the righting reflex recovered, the mice were immediately put back into the normoxic environment for feeding by their mothers.The respiratory rate (RR) and blood oxygen saturation (SpO2) of immature SD rats were observed and monitored after propofol anesthesia.The morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy.The contents of Fe2+ and malondialdehyde (MDA) in the hippocampus were detected by biochemical assay, and the protein expression of transferrin receptor (TFRC) in the hippocampus was detected by Western blotting. Results The results of RR and SpO2 monitoring showed that compared with the corresponding lipid emulsion group, only RR in the PO group was decreased (CO vs PO, P < 0.01), while RR and SpO2 in the PA and PH groups were decreased (CA vs PA, CH vs PH, P < 0.01).Transmission electron microscopy displayed that the mitochondria in the hippocampal neurons of the PA and PH groups were generally swollen, with dissolved and disappeared mitochondrial cristae.The results of the biochemical assay showed that the Fe2+ content and MDA level in the PO, PA, and PH groups were increased than those in the corresponding lipid emulsion groups (P < 0.01).Compared with the PO group, the content of Fe2+ and MDA were increased in the PA and PH groups (P < 0.05).Western blotting indicated that compared with the corresponding lipid emulsion group, the expression level of TFRC in the PO, PA, and PH groups was increased (P < 0.05), while the level was increased in the PA and PH groups than the PO group (P < 0.05). Conclusion Hypoxia aggravates the damage of hippocampal neurons induced by propofol in immature SD rats, and the mechanism is related to the ferroptosis of hippocampal tissue.
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