上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2026 , Vol. 46 >Issue 3: 301 - 311

DOI: https://doi.org/10.3969/j.issn.1674-8115.2026.03.004

论著 · 基础研究

天麻素调控自噬在心肌梗死后骨骼肌萎缩中的作用研究

  • 徐州琳 ,
  • 尹高生 ,
  • 李沅聪 ,
  • 杨云恒 ,
  • 郑琦 ,
  • 杨萍
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  • 1.昆明医科大学康复学院云南省干细胞和再生医学重点实验室，昆明 650500
    2.昆明医科大学第一附属医院肾脏内一科，昆明 650032
    3.昆明医科大学第二附属医院心血管内科三病区，昆明 650101
杨　萍，副教授，硕士；电子信箱：yangping871022@126.com。

收稿日期: 2025-07-31

  录用日期: 2026-01-21

  网络出版日期: 2026-03-30

基金资助

云南省科技厅-昆明医科大学应用基础研究联合专项(2024AY070001-075)

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Study on the role of gastrodin-mediated autophagy in skeletal muscle atrophy after myocardial infarction

  • Xu Zhoulin ,
  • Yin Gaosheng ,
  • Li Yuancong ,
  • Yang Yunheng ,
  • Zheng Qi ,
  • Yang Ping
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  • 1.Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming 650500, China
    2.Division One of Nephrology Department, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
    3.Division Three of Cardiovascular Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
YANG Ping, E-mail: yangping871022@126.com.

Received date: 2025-07-31

  Accepted date: 2026-01-21

  Online published: 2026-03-30

Supported by

Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Fund for Applied Basic Research(2024AY070001-075)

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摘要

目的·观察心肌梗死（myocardial infarction，MI）4周后骨骼肌萎缩的发生情况，并进一步明确天麻素（gastrodin，Gas）对MI后心肌损伤和骨骼肌萎缩的作用及机制。方法·选取健康成年雄性SD大鼠构建动物模型，随机分为假手术组（Sham）、MI模型组和MI+Gas治疗组，每组10只。采用血管紧张素Ⅱ（angiotensin Ⅱ，AngⅡ）刺激心肌成纤维细胞（cardiac fibroblasts，CFs）的条件培养基培养L6骨骼肌肌管细胞（L6 myotubes，L6，模型细胞），并分为对照组（Control）、模型组（Model）、天麻素治疗组（Treatment）、氯喹（chloroquine，CQ）处理组（Treatment+CQ）共4组。分别采用M型超声心动图、Masson三色染色及苏木精-伊红（hematoxylin-eosin staining，HE）染色检测3组大鼠的心功能、心肌纤维化情况、胫骨前肌肌束横截面积与肌束数量。采用蛋白质印迹法（Western blotting）分别检测3组大鼠组织和4组L6肌管细胞的成肌分化蛋白（myoblast determination protein，MyoD）、肌生成素（myogenin，MyoG）、肌环指蛋白1（muscle Ring finger-1，MuRF-1）、肌肉萎缩F盒蛋白（muscle atrophy F-box protein，MAFbx）、自噬效应蛋白（Beclin-1）、选择性自噬衔接蛋白（sequestosome-1，p62/SQSTM1）、微管相关蛋白1轻链3-Ⅰ/Ⅱ（microtubule-associated protein 1 light chain 3-Ⅰ/Ⅱ，LC3-Ⅰ/Ⅱ）的表达水平。采用mRFP-eGFP-LC3慢病毒转染L6成肌细胞，检测对照组（Control）、模型组（Model）、天麻素治疗组（Treatment）细胞的自噬流情况。结果·与MI组相比，MI+Gas治疗组大鼠的心功能指标改善，心肌纤维化程度降低，胫骨前肌横截面积增加、肌束数量减少。从骨骼肌组织和L6肌管细胞层面证实，Gas干预可促进肌生成相关蛋白MyoD、MyoG的表达，抑制骨骼肌萎缩相关蛋白MuRF-1、MAFbx的表达（分别较MI/Model组，均P<0.05）；Gas可降低自噬相关蛋白Beclin-1、LC3-Ⅱ/GAPDH的表达（分别较MI/Model组，均P<0.001），并上调p62的表达（P=0.036），改善骨骼肌自噬流。与Treatment组相比，加入CQ预处理可逆转Gas对成肌标志物、萎缩标志物的调节作用。结论·MI诱导骨骼肌萎缩，而Gas可改善MI后的心功能不良和骨骼肌萎缩，并通过恢复自噬流以调节骨骼肌合成与分解代谢平衡。

关键词： 心肌梗死; 骨骼肌萎缩; 天麻素; 自噬流; 能量代谢

本文引用格式

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 . DOI: 10.3969/j.issn.1674-8115.2026.03.004

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.

Key words： myocardial infarction (MI); skeletal muscle atrophy; gastrodin (Gas); autophagic flux; energy metabolism

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