Regulatory role of the peroxisome proliferator-activated receptor gamma-nuclear factor erythroid 2-related factor 2-heme oxygenase-1 signaling pathway in ferroptosis in the hippocampal tissue of rats with status epilepticus

Objective To investigate the regulatory role of the peroxisome proliferator-activated receptor gamma (PPARγ)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in ferroptosis in the hippocampal tissue of rats with status epilepticus (SE). Methods A total of 57 male Wistar rats were selected, among which 47 rats were randomly selected and were given intraperitoneal injection of lithium chloride, scopolamine hydrobromide, and pilocarpine to induce SE, and the remaining 10 rats were included as control group and were given intraperitoneal injection of an equal volume of normal saline. The Racine scale was used to assess the severity of seizure, and the rats with stage Ⅳ or higher seizures and a duration of >60 minutes were selected and randomly divided into SE group, activator group, and inhibitor group, with 10 rats in each group. The rats in the activator group were given injection of the PPARγ agonist rosiglitazone, while those in the inhibitor group were given injection of the PPARγ inhibitor T0070907; the rats in the control group and the SE group were given injection of an equal dose of normal saline. Intraperitoneal injection was performed once every other day for 21 days. On day 22, the rats were sacrificed and hippocampal tissue was dissected. A transmission electron microscope was used to observe mitochondrial ultrastructure in hippocampal tissue of rats in the control group and the SE group; RT-qPCR and Western blot were used to measure the relative mRNA and protein expression levels of PPARγ, Nrf2, HO-1, and glutathione peroxidase 4 (Gpx4) in the hippocampal tissue of rats in each group; colorimetry was used to measure the levels of Fe2+, glutathione (GSH), and malondialdehyde (MDA) in the hippocampal tissue of rats in each group. Results Compared with the control group, the SE group had reductions in mitochondrial vo-lume and mitochondrial cristae, significant increases in the levels of Fe2+ and MDA and the relative mRNA and protein expression levels of PPARγ, Nrf2, and HO-1, and significant reductions in the level of GSH and the relative mRNA and protein expression levels of Gpx4 (F=28.090-153.500,t=12.350,2.355,q=6.216-20.510,P