中国药物警戒 ›› 2026, Vol. 23 ›› Issue (7): 757-766.
DOI: 10.19803/j.1672-8629.20260168

• 蒙药干预高血压性心肌肥厚的机制研究专栏 • 上一篇    下一篇

蒙药四味土木香散调控代谢网络改善压力超负荷性心肌肥厚的作用机制

郭颖1,2, 郭玉婷1,2, 尹东杰1,2, 任中杰1,2, 董娜1,2, 魏明慧3, 鲁子瑜1,2, 李祥名1, 王敏杰1, 薛明明1,*   

  1. 1内蒙古医科大学基础医学院,内蒙古 呼和浩特 010059;
    2内蒙古医科大学基础医学院医学神经生物学实验室,内蒙古 呼和浩特 010059;
    3内蒙古医科大学实验室与实验设备管理中心,内蒙古 呼和浩特 010059
  • 收稿日期:2026-03-02 出版日期:2026-07-15 发布日期:2026-07-16
  • 通讯作者: *薛明明,女,博士,教授,心血管生理学。E-mail:happybird-nmg@163.com
  • 作者简介:郭颖,女,硕士,心血管生理学。
  • 基金资助:
    国家自然科学基金资助项目(82360095); 内蒙古医科大学大学生创新创业训练计划项目(202510132001、S202510132013); 内蒙古自治区自然科学基金资助项目(2022LHMS08002); 内蒙古自治区高等学校创新团队发展计划项目(NMGIRT2420); 内蒙古医科大学科技创新团队项目(YKD2024TD001); 内蒙古自然科学基金资助项目(2026ZD038)

Mongolian medicine Siwei Tumuxiang powder ameliorates pressure overload-induced cardiac hypertrophy by regulating metabolic networks

Guo Ying1,2, Guo Yuting1,2, Yin Dongjie1,2, Ren Zhongjie1,2, Dong Na1,2, Wei Minghui3, Lu Ziyu1,2, Li Xiangming1, Wang Minjie1, Xue Mingming1,*   

  1. 1School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot Inner Mongolia 010059, China;
    2Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot Inner Mongolia 010059, China;
    3Laboratory and Experimental Equipment Management Center, Inner Mongolia Medical University, Hohhot Inner Mongolia 010059, China
  • Received:2026-03-02 Online:2026-07-15 Published:2026-07-16

摘要: 目的 研究蒙药四味土木香散(Siwei Tumuxiang Powder, STP)对腹主动脉缩窄(Abdominal Aortic Constriction, AAC)诱导的压力超负荷性心肌肥厚(Pressure Overload-Induced Cardiac Hypertrophy, POH)大鼠的保护作用,并从代谢组学层面探讨其作用机制。方法 40只雄性SD大鼠随机分为假手术(Sham-Operated,Sham)组、模型(Model,Mod)组、STP组(1.6 g·kg-1)和阳性药卡托普利(Captopril, CAP)组(0.015 g·kg-1),AAC术后灌胃给药4周。超声心动图检测心功能,苏木精-伊红(Hematoxylin-Eosin Staining, HE)染色和Masson染色观察心肌病理变化,RT-qPCR和Western Blot检测心肌肥厚及纤维化标志物表达。采用超高效液相色谱-四级杆飞行时间质谱(UPLC-Q-TOF/MS)非靶向代谢组学结合加权基因共表达网络分析(Weighted Gene Co-Expression Network Analysis, WGCNA)筛选关键代谢物及通路。结果 与Mod组相比,STP干预可显著降低AAC大鼠的前壁厚度(AWT)和后壁厚度(PWT),提高射血分数(EF%)和短轴缩短率(FS%),改善心功能;减轻心肌细胞水肿、纤维排列紊乱及胶原沉积;下调ANP、β-MHC、TGF-β和Col-1的mRNA及蛋白表达水平。代谢组学分析共识别出5个与疾病及药物干预密切相关的核心代谢模块,筛选出52个Hub代谢物,其中39个与疾病高度相关;KEGG通路富集分析显示,这些Hub代谢物主要富集于核黄素代谢、咖啡因代谢和亚油酸代谢等通路。结论 STP对AAC诱导的POH具有显著保护作用,其机制与调控核黄素代谢改善线粒体能量供应、咖啡因代谢维持嘌呤稳态及亚油酸代谢抑制炎症纤维化密切相关,体现了蒙药复方多成分-多靶点-网络调控的特点。

关键词: 四味土木香散, 压力超负荷性心肌肥厚, 超高效液相色谱-四级杆飞行时间质谱(UPLC-Q-TOF/MS), 非靶向代谢组学, 大鼠

Abstract: Objective To investigate the cardioprotective effects of the Mongolian medicine Siwei Tumuxiang powder (STP) against pressure overload-induced cardiac hypertrophy (POH) resulting from abdominal aortic constriction (AAC) in rats, and to explore its underlying mechanism using metabolomics. Methods Forty male Sprague-Dawley rats were randomly divided into four groups: sham-operated (Sham), model (Mod), STP (1.6 g·kg-1), and the positive control captopril (CAP) group (0.015 g·kg-1). Following AAC surgery, the rats received intragastric administration of the respective drug for four weeks. Cardiac function was recorded using echocardiography. Myocardial pathological changes were observed via Hematoxylin-Eosin and Masson staining. The expression levels of markers for cardiac hypertrophy and fibrosis were detected using RT-qPCR and Western blot. Untargeted metabolomics based on UPLC-Q-TOF/MS was employed in combination with weighted gene co-expression network analysis (WGCNA) to screen out key metabolites and pathways. Results Compared to the Mod group, STP inter-vention significantly reduced the anterior wall thickness (AWT) and posterior wall thickness (PWT), increased ejection fraction (EF) and fractional shortening (FS), thereby improving cardiac function in AAC rats. STP also mitigated myocardial cell edema, disordered fiber arrangement, and collagen deposition. Furthermore, STP downregulated the mRNA and protein expression levels of ANP, β-MHC, TGF-β, and Col-1. Metabolomics analysis identified five core metabolic modules closely associated with both the disease state and drug intervention, leading to the selection of 52 hub metabolites, 39 of which were closely correlated with the disease. KEGG pathway enrichment analysis revealed that these hub metabolites were primarily enriched in such pathways as riboflavin metabolism, caffeine metabolism, and linoleic acid metabolism. Conclusions TP exerts a significant protective effect against AAC-induced POH, which is closely associated with its ability to improve mitochondrial energy supply by regulating riboflavin metabolism, to maintain purine homeostasis by regulating caffeine metabolism, and to inhibit inflammation and fibrosis by inhibiting linoleic acid metabolism. This study highlights the multi-component, multi-target, and network-regulating properties of this Mongolian medicinal compound.

Key words: Siwei Tumuxiang Powder, Pressure Overload-Induced Cardiac Hypertrophy, UPLC-Q-TOF/MS, Untargeted Metabolomics, Rats

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