南方医科大学学报2026，Vol.46Issue(4)：803-815,13.DOI:10.12122/j.issn.1673-4254.2026.04.09
麦冬皂苷D通过激活β-catenin/FUNDC1/线粒体自噬轴减轻阿霉素诱导的小鼠心肌肥厚
Ophiopogonin D alleviates doxorubicin-induced myocardial hypertrophy in mice by activating the β-catenin/FUNDC1/mitophagy axis
摘要
Abstract
Objective To investigate whether ophiopogonin D(OD)alleviates doxorubicin(Dox)-induced myocardial hypertrophy in mice by regulating the β-catenin/FUNDC1/mitophagy signaling axis.Methods Thirty C57BL/6J mice were randomized equally into control group,Dox treatment group,Dox with OD treatment group,Dox treatment group with injection of adeno-associated virus(AAV)vector carrying β-catenin,and Dox treatment group with injection of AAV vector.RNA sequencing analysis was used to identify differentially expressed genes in cultured mouse cardiac cells following Dox treatment.Western blotting was performed to examine the protein levels of β-catenin,active β-catenin,FUNDC1,LC3,p62,β-myosin heavy chain(β-MHC),and α-actin;immunohistochemistry and immunofluorescence staining were used to assess the localization and expression of β-catenin and FUNDC1.Transmission electron microscopy was employed to evaluate mitochondrial damage in the cardiac myocytes.Chromatin immunoprecipitation and dual-luciferase reporter gene assays were used to investigate the transcriptional regulation of FUNDC1 by β-catenin.Results Dox treatment significantly inhibited β-catenin signaling and FUNDC1-mediated mitophagy,leading to cardiomyocyte hypertrophy and mitochondrial damage.OD treatment obviously reversed these effects,restored β-catenin signaling,enhanced FUNDC1 transcription and expression,and promoted mitophagy.Overexpression of β-catenin or FUNDC1 mimicked the cardioprotective effect of OD,while knockdown of β-catenin aggravated myocardial hypertrophy,which was reversed by FUNDC1 overexpression.Mechanistically,β-catenin directly bound to the FUNDC1 promoter and activated its transcription.Conclusion OD alleviates Dox-induced myocardial hypertrophy in mice by activating the β-catenin/FUNDC1/mitophagy axis and enhancing mitochondrial quality control.关键词
麦冬皂苷D/心肌肥厚/β-catenin/线粒体自噬/阿霉素Key words
ophiopogonin D/myocardial hypertrophy/β-catenin/mitophagy/doxorubicin引用本文复制引用
雷艳萍,宋嘉晟,徐乐吾,刘睿,赵岳..麦冬皂苷D通过激活β-catenin/FUNDC1/线粒体自噬轴减轻阿霉素诱导的小鼠心肌肥厚[J].南方医科大学学报,2026,46(4):803-815,13.基金项目
湖南省自然科学基金(2021JJ40476,2021JJ40506) （2021JJ40476,2021JJ40506）
