Psoralen attenuates propofol-induced neurotoxicity in young rats by regulating the Keap1/Nrf2 pathway
Objective To investigate the protective effects and mechanisms of psoralen on neurotoxicity in juvenile rats.Methods Hippocampal cell line HT22 cells were incubated with 100 μmol/L propofol for 6 hours to induce cell inflam-mation.The experiment included control group,propofol group,propofol+psoralen(1,5,10 μmol/L)groups,and propofol+psoralen(10 μmol/L)+Keap1/Nrf2 pathway inhibitor(KI696,5 μmol/L)group.Cell viability was tested by CCK8 assay,and apoptosis was detected by flow cytometry.Juvenile SD rats were randomly divided into control group(C group),propofol group(P group),propofol+psoralen group(PP group),and propofol+psoralen+KI696 group(PPI group).P group rats were intraperitoneally injected with propofol 50 mg/kg,PP group with propofol and psoralen 20 mg/kg,and PPI group with propo-fol,psoralen,and KI696 30 μmol/kg.Hippocampal tissue pathological changes were observed using Nissl staining.Inflam-matory responses(IL-6 and TNF-α levels)and oxidative stress(MDA content,SOD,and GSH activity)in cells and tissues were measured by ELISA,and Keap1 and Nrf2 protein expression was detected by Western blot.Results Compared to the control group,the HT22 cell viability in the propofol-treated group was significantly reduced,and cell apoptosis,Keap1 pro-tein level,inflammatory response and oxidative stress were significantly increased(P＜0.05).Psoralen treatment improved cell neuroinflammation and oxidative stress in a dose-dependent manner(P＜0.05),and KI696 treatment reversed the protective effects of psoralen on cell functions.Compared to the C group,hippocampal inflammation and oxidative stress in the P group rats worsened.Psoralen treatment alleviated neuronal damage in rat hippocampal tissue.Conclusion Psoralen alleviates pro-pofol-induced neurotoxicity in young rats by activating the Keap1/Nrf2 pathway.
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