Study on the mechanism of astragalus glycyrrhiza decoction regulat-ing SIRT1/FOXO1 pathway to prevent QT interval prolongation in-duced by arsenic trioxide based on metabolomics
AIM:To explore the protective effect of astragalus glycyrrhiza decoction(AGD)on arsenic trioxide(ATO)-induced QT interval prolongation and its mechanism based on metabonomics.METH-ODS:The model of ATO-induced QT interval prolon-gation in rats was established,and ECG,blood rou-tine,and metabonomics were detected,and the key targets were collected combined with network pharmacology.The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro.RESULTS:AGD could significantly alleviate the ATO-induced QT interval of SD rats.GO enrichment analysis was mainly related to inflammatory response,reactive oxygen species,oxidative stress,inner cell vesicles,folds,inner cell vesicles,SMAD binding,R-SMAD binding,and signal receptor activator activity.KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway,lipid and arteriosclero-sis,FOXO signal pathway,TNF signal pathway,HIF-1,and other signal pathways.Through the H9c2 cell model in vitro,it was verified that AGD could reverse the expression of SIRT1 and FOXO1 pro-teins.CONCLUSION:AGD may improve the ATO-in-duced QT interval prolongation and reduce the car-diotoxicity of ATO by regulating the SIRT1/FOXO1 signal pathway.
万方数据
维普
