上海交通大学学报(医学版)2026,Vol.46Issue(3):301-311,11.DOI:10.3969/j.issn.1674-8115.2026.03.004
天麻素调控自噬在心肌梗死后骨骼肌萎缩中的作用研究
Study on the role of gastrodin-mediated autophagy in skeletal muscle atrophy after myocardial infarction
摘要
Abstract
Objective·To observe the occurrence of skeletal muscle atrophy at 4 weeks after myocardial infarction(MI),and to further investigate the therapeutic effects and underlying mechanisms of gastrodin(Gas)on post-MI cardiac injury and skeletal muscle atrophy.Methods·In vivo,healthy adult male Sprague-Dawley(SD)rats were selected to establish animal models and were randomly divided into a sham operation group(Sham),MI model group(MI),and MI+Gas treatment group(MI+Gas),with 10 rats in each group.In vitro,L6 myotubes were cultured with conditioned medium from angiotensin II(AngII)-stimulated cardiac fibroblasts(CFs),and were divided into a control group(Control),model group(Model),gastrodin treatment group(Treatment),and chloroquine(CQ)treatment group(Treatment+CQ).Cardiac function,myocardial fibrosis,and the cross-sectional area and number of tibialis anterior muscle fibers in rats from the three groups were evaluated by M-mode echocardiography,Masson's trichrome straining,and hematoxylin-eosin(HE)staining,respectively.Protein expression levels of myoblast determination protein(MyoD),myogenin(MyoG),muscle Ring finger-1(MuRF-1),muscle atrophy F-box protein(MAFbx),Beclin-1,sequestosome-1(p62/SQSTM1),and microtubule-associated protein 1 light chain 3-Ⅰ/Ⅱ(LC3-Ⅰ/Ⅱ)in tissues from the three groups and in L6 myotube groups were detected by Western blotting.L6 myoblasts were transfected with mRFP-eGFP-LC3 lentivirus to measure autophagic flux in the Control,Model,and Treatment groups.Results·Compared with the MI group,the MI+Gas group showed significantly improved cardiac function,reduced myocardial fibrosis,increased cross-sectional area of tibialis anterior muscle fibers,and decreased number of tibialis anterior muscle fibers.At both the skeletal muscle tissue and L6 myotube levels,Gas treatment promoted the expression of myogenesis-related proteins MyoD and MyoG,and inhibited the expression of skeletal muscle atrophy-related proteins MuRF-1 and MAFbx(vs.MI/Model group,P<0.05).Gas also reduced the expression of autophagy-related proteins Beclin-1 and LC3-Ⅱ/GAPDH(vs.MI/Model group,P<0.001),increased p62 expression(P=0.036),and improved skeletal muscle autophagic flux.Compared with the Treatment group,CQ pretreatment reversed the regulatory effects of Gas on myogenic and atrophy markers.Conclusion·This study confirms that MI induces skeletal muscle atrophy,while Gas ameliorates post-MI cardiac dysfunction and skeletal muscle atrophy by restoring autophagic flux to regulate metabolic balance.关键词
心肌梗死/骨骼肌萎缩/天麻素/自噬流/能量代谢Key words
myocardial infarction(MI)/skeletal muscle atrophy/gastrodin(Gas)/autophagic flux/energy metabolism分类
医药卫生引用本文复制引用
徐州琳,尹高生,李沅聪,杨云恒,郑琦,杨萍..天麻素调控自噬在心肌梗死后骨骼肌萎缩中的作用研究[J].上海交通大学学报(医学版),2026,46(3):301-311,11.基金项目
云南省科技厅-昆明医科大学应用基础研究联合专项(2024AY070001-075). Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Fund for Applied Basic Research(2024AY070001-075). (2024AY070001-075)