南方医科大学学报2025，Vol.45Issue(9)：1850-1858,9.DOI:10.12122/j.issn.1673-4254.2025.09.05
橙皮素通过调控AMPK/NLRP3通路减轻阿霉素诱导的小鼠心肌毒性
Hesperetin alleviates doxorubicin-induced cardiotoxicity by regulating the AMPK/NLRP3 pathway
摘要
Abstract
Objective To verify whether hesperetin(Hes)alleviates doxorubicin(DOX)-induced cardiotoxicity by reducing inflammation via regulating the AMPK/NLRP3 pathway.Methods C57/bl6 mice and H9c2 cells treated with DOX to mimic cardiotoxicity were randomly divided into Sham(or control)group,DOX group,DOX+Hes group,DOX+Hes+compound C(CC,an AMPK inhibitor)group.Cardiac function and myocardial pathologies of the mice were evaluated,and the changes in H9c2 cell morphology and viability were assessed.Lactate dehydrogenase(LDH)activity in mouse myocardial tissues and H9c2 cells was measured using ELISA,and H9c2 cell apoptosis was detected with TUNEL staining.In both H9c2 cells and the myocardial tissues of the mice,cellular expression levels of TNF-α,IL-6 and IL-1β mRNAs and cleaved caspase-3,Bcl2,Bax,IL-1β,IL-18,p-AMPK,AMPK,p-mTOR,mTOR,NLRP3,ASC and caspase-1 proteins were detected using RT-PCR and Western blotting.Results DOX treatment caused cell swelling,decreased cell viability and increased LDH activity in H9c2 cells,resulting also in significantly increased cell apoptosis and cleaved caspase-3 expression and decreased Bcl2/Bax ratio.The DOX-treated mice showed obvious myocardial fiber swelling and inflammatory infiltration,decreased cardiac function and significantly increased myocardial LDH activity.In H9c2 cells,DOX treatment significantly increased the mRNA expressions of TNF-α,IL-6 and IL-1β and protein expressions of IL-1β and IL-18,lowered the expressions of p-AMPK and p-mTOR,and increased the expressions of NLRP3,ASC and caspase-1.Hes treatment obviously reduced these toxic effects of DOX in H9c2 cells,but its protective effects were blocked by application of compound C.Conclusion Hes reduces DOX-induced cardiotoxicity by inhibiting inflammation via regulating the AMPK/NLRP3 pathway.关键词
橙皮素/阿霉素/AMPK/NLRP3/炎症反应/H9c2细胞Key words
hesperetin/doxorubicin/AMPK/NLRP3/inflammatory response/H9c2 cells引用本文复制引用
闫爱丽,罗梦瑶,常晋瑞,李新华,朱娟霞..橙皮素通过调控AMPK/NLRP3通路减轻阿霉素诱导的小鼠心肌毒性[J].南方医科大学学报,2025,45(9):1850-1858,9.基金项目
陕西省教育厅专项科研计划项目(20JK0883,20JS135) （20JK0883,20JS135）
