Protective effect of Eriodictyol on cerebral ischemia/reperfusion injury in rats by regulating PPARδ expression
Objective:To study the protective effect of Eriodictyol preconditioning on cerebral ischemia/reperfusion(I/R)injury in rats and its mechanism.Methods:Ninety SD rats were randomly divided into sham operation group,model group,Eriodictyol low-dose group(17.5 mg/kg),Eriodictyol medium-dose group(35 mg/kg),Eriodictyol high-dose group(70 mg/kg)and high-dose group+peroxisome proliferator-activated receptors δ(PPARδ)antagonist GSK3787 group(70 mg/kg Eriodictyol+300 μg/kg GSK3787),with 15 rats in each group.Rat model of cerebral I/R was established by bilateral common carotid artery occlusion combined with hypoten-sion.Before modeling,different doses of Eriodictyol or GSK3787 were used to intervene rats.After 24 hours of I/R,the signs of neuro-logical deficit were scored;the area of cerebral infarction in rats were observed by TTC staining;pathological changes of cerebral cortex was observed by HE staining;content of MDA and activity of SOD in cerebral cortex were detected by biochemical method;levels of IL-1β,IL-6 and TNF-α in cerebral cortex were detected by ELISA;protein expression levels of PPARδ,PPARγ coactivator-1α(PGC-1α)and NF-κB p65 in cerebral cortex were detected by Western blot.Results:Compared with sham operation group,pathological injury of brain tissue was serious,the sign score of neurological deficit,the area of cerebral infarction and contents of MDA,IL-1β,IL-6 and TNF-α in model group were increased significantly(P<0.05),while activity of SOD and protein expression levels of PPARδ and PGC-1α were decreased significantly(P<0.05),meanwhile,protein expression level of NF-κB p65 was increased significantly(P<0.05).Compared with model group,pathological injury of brain tissue was reduced,the sign score of neurological deficit,cerebral infarcition area and contents of MDA,IL-1β,IL-6 and TNF-α in cerebral cortex of rats in different concentrations of Eriodictyol groups were decreased significantly(P<0.05),activity of SOD and protein expression levels of PPARδ and PGC-1α were increased signifi-cantly(P<0.05),meanwhile,protein expression level of NF-κB p65 was decreased significantly(P<0.05).Compared with Eriodic-tyol high-dose group,GSK3787 combined intervention could significantly reduce the protective effect of Eriodictyol on cerebral I/R in-jury in rats(P<0.05).Conclusion:Eriodictyol preconditioning has a good protective effect on cerebral I/R injury,and its mechanism may be related to the activation of PPARδ/PGC-1α signaling pathway.
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