文献类型：期刊文献

中文题名：基于代谢组学研究黄芪甘草汤调控SIRT1/FOXO1通路预防三氧化二砷诱导的QT间期延长的作用机制

英文题名：Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1/FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics

作者：徐兰[1];海洋[2];任珂[1];张雅荣[1];曹浩时[1];刘东玲[1]

第一作者：徐兰

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]甘肃中医药大学科研实验中心,甘肃兰州730000

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2024

卷号：29

期号：2

起止页码：130

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金(82260792);甘肃省高等学校青年博士基金项目(22QB-101);甘肃省高等学校创新基金项目(2019YJRC-02);甘肃省科技计划项目(创新基地和人才计划)(21JR11RA148)。

语种：中文

中文关键词：黄芪甘草汤;三氧化二砷;QT间期;代谢组学

外文关键词：astragalus glycyrrhiza decoction;arse-nic trioxide;QT interval;metabolomics

摘要：目的:基于代谢组学探索黄芪甘草汤防治三氧化二砷诱导QT间期延长的保护作用及其机制。方法:建立三氧化二砷诱导大鼠QT间期延长模型。检测大鼠心电图、血常规、代谢组学差异代谢物,并结合网络药理学收集关键靶点,通过功能注释、通路富集分析筛选黄芪甘草汤保护作用的可能候选基因与通路,并进行体外实验验证。结果:黄芪甘草汤对三氧化二砷诱导的SD大鼠QT间期具有显著的缓解作用(P<0.05);GO富集分析发现黄芪甘草汤和三氧化二砷诱导QT间期延长的关键靶点主要涉及炎症应答、活性氧、氧化应激等生物过程,内细胞囊泡、褶皱、内细胞囊泡膜等细胞组分,SMAD结合、R-SMAD结合、信号受体激活剂的活性等分子功能;KEGG通路分析发现其主要富集于PI3K-Akt信号通路、脂质和动脉硬化、FOXO信号通路、TNF信号通路、HIF-1等信号通路。通过体外H9c2细胞模型,验证了黄芪甘草汤能够逆转SIRT1、FOXO1蛋白表达。结论:黄芪甘草汤可能通过调控SIRT1/FOXO1信号通路,从而改善三氧化二砷诱导QT间期延长,减轻三氧化二砷心脏毒性。
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.