Exploring the effect of hydroxysafflor yellow A on autophagy and apoptosis in cerebrovascular endothelial cells based on silent information regulator 1/forkhead box protein O3A signal pathway
Objective:To investigate the effects of hydroxysafflor yellow A (HSYA) on autophagy and apoptosis in cerebrovascular endothelial cells through silent information regulator 1 ( SIRT1 )/forkhead box protein O3A (FOXO3A) signaling pathway.Methods:In vivo experiments were conducted using middle cerebral artery occlusion ( MCAO) model,using SD rats randomly divided into Sham group,MCAO group,and MCAO+HSYA group.In vitro experiments were conducted using an oxygen-glucose deprivation ( OGD) model using cells randomly divided into Normal group,OGD group,OGD+HSYA group,OGD+EX-527 group and OGD+EX-527+HSYA group.The experiment used Z-Longa method,TTC staining,TUNEL staining,flow cytometry,immunofluorescence,Western blot,and RT-qPCR to detect relevant indicators.Results:In vivo experimental,compared with the Sham group,the MCAO group showed an increase in neurological function score and cerebral infarction area,a decrease in the expression of sequestosome 1 (P62),SIRT1,and FOXO3A proteins,and an increase in the number of apoptotic cells,microtubule-associated protein 1 light chain 3 (LC3) protein,and fluorescent spots (P<0.05);Compared with the MCAO group,the MCAO+HSYA group showed a significant decrease in neurological function score and infarct size,as well as a decrease in P62 protein expression and apoptosis count.The expression of LC3,SIRT1,FOXO3A proteins,and LC3 fluorescence spot count increased (P<0.05).In vitro experimental,compared with the Normal group,the OGD group showed a decrease in P62,SIRT1,FOXO3A mRNA and protein expression,an increase in cell apoptosis rate,LC3 mRNA,LC3 protein,and fluorescence spot number (P<0.05);Compared with the OGD group,the OGD+HSYA group showed a decrease in cell apoptosis rate,P62 mRNA and protein expression,and an increase in LC3,SIRT1,FOXO3A mRNA and protein expression,as well as LC3 fluorescence spot number expression (P<0.05);Compared with the OGD+EX-527 group,the OGD+EX-527+HSYA group showed a decrease in P62 mRNA and protein expression levels and cell apoptosis rate,while the expression of LC3,SIRT1,FOXO3A mRNA and protein,and LC3 fluorescence spot number increased (P<0.05).Conclusion:HSYA activates cerebrovascular endothelial cell autophagy by activating SIRT1/FOXO3 A signaling pathway and reduces the apoptosis of cerebrovascular endothelial cells.
silent information regulator 1/forkhead box protein O3A signaling pathwayhydroxysafflor yellow Acerebrovascular endothelial cellsautophagyapoptosis
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维普
