中国药物警戒 ›› 2026, Vol. 23 ›› Issue (1): 42-49.
DOI: 10.19803/j.1672-8629.20250594

• 蒙药药效物质基础与作用机制研究专栏 • 上一篇    下一篇

基于组织非靶向代谢组学探究四味土木香散治疗高血压性心肌肥厚的作用机制

任中杰1,2, 魏明慧3, 尹东杰1,2, 郭颖1,2, 鲁子瑜1,2, 于洋1, 郭玉婷1,2, 张欣1, 刘芳冰4, 张佳茹4, 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;
    4内蒙古医科大学第二附属医院,内蒙古 呼和浩特 010110
  • 收稿日期:2025-08-26 出版日期:2026-01-15 发布日期:2026-01-15
  • 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:任中杰,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); 内蒙古自治区自然科学基金资助项目(2022LHMS08002、2020MS08139); 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)

Treatment of Hypertensive Cardiac Hypertrophy with Siwei Tumuxiang Powder Based on Tissue Non-Targeted Metabolomics

REN Zhongjie1,2, WEI Minghui3, YIN Dongjie1,2, GUO Ying1,2, LU Ziyu1,2, YU Yang1, GUO Yuting1,2, ZHANG Xin1, LIU Fangbing4, ZHANG Jiaru4, 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;
    4The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China
  • Received:2025-08-26 Online:2026-01-15 Published:2026-01-15

摘要: 目的 探究四味土木香散(Siwei Tumuxiang Powder, STP)对大鼠高血压性心肌肥厚(Hypertensive Cardiac Hypertrophy, HCH)的干预机制。方法 40只SD大鼠随机分成4组,分别是假手术(Sham-Operated, Sham)组、模型(Model, Mod)组、四味土木香散(Siwei Tumuxiang Powder, STP)组(1.6 g·kg-1)、阳性药卡托普利(Captopril, CAP)组(0.015 g·kg-1),每组各10只。Mod组、STP组和CAP组利用腹主动脉缩窄术(Abdominal Aortic Coarctation, AAC)诱导构建高血压性心肌肥厚模型,Sham组只分离腹主动脉不结扎。在造模同时对STP组、CAP组分别给予STP、CAP干预8周,Sham组给予0.9%氯化钠溶液灌胃。8周后,通过超声心动图检测各组大鼠的心功能,苏木精-伊红染色(Hematoxylin-Eosin Staining, HE)、Masson染色观察大鼠心脏组织的病理变化,采用实时荧光定量聚合酶链反应(Real-Time Quantitative Polymerase Chain Reaction, RT-qPCR)检测心肌肥厚标志物β-肌球蛋白重链(Myosin Heavy Chain Beta, β-MHC)和心肌纤维化标志物转化生长因子-β(Transforming Growth Factor-β, TGF-β)mRNA表达水平,用蛋白免疫印迹(Western Blot, WB)法检测β-MHC TGF-β蛋白表达水平,随后进行代谢组学检测。结果 与Sham组相比,Mod组大鼠心室壁增厚、心功能降低、出现心肌纤维化及炎症浸润,β-MHC和TGF-β的基因与蛋白表达水平均有所升高。而与Mod组相比,STP组HCH大鼠心室壁厚度、心功能、心肌纤维化及炎症浸润得到显著改善,心肌肥厚及心肌纤维化标志物的基因与蛋白表达得到下调。非靶向代谢组学筛选出13种差异代谢物,涉及花生四烯酸代谢、三羧酸循环等14条通路。结论 STP通过多靶点干预心肌肥厚及代谢紊乱,可能通过调节能量代谢、抑制炎症反应等发挥治疗作用。

关键词: 高血压性心肌肥厚, 腹主动脉缩窄, 四味土木香散, 非靶向代谢组学, 大鼠

Abstract: Objective To investigate the mechanism through which Siwei Tumuxiang powder (STP) intervenes in hypertensive cardiac hypertrophy (HCH) in rats. Methods Forty Sprague-Dawley (SD) rats were randomly divided into four groups (n=10 each): the sham-operated (Sham) group, model (Mod) group, STP group (1.6 g·kg-1), and positive control captopril (CAP) group (0.015 g·kg-1). The last three groups underwent abdominal aortic coarctation (AAC) to induce HCH while the Sham group received abdominal aortic isolation without ligation. Concurrently, the STP and CAP groups were subjected to eight weeks of interventions with STP and CAP, whereas the Sham and Mod groups received 0.9% saline solution via gavage. After 8 weeks, cardiac function was assessed using echocardiography. Pathological changes in cardiac tissues were observed using hematoxylin-eosin (HE) and Masson staining. The mRNA expression levels of hypertrophy markers β-myosin heavy chain (β-MHC) and the myocardial fibrosis marker transforming growth factor-β (TGF-β) were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Protein expression levels of β-MHC and TGF-β were determined by Western blot (WB). Additionally, metabolomic analysis was conducted. Results Compared to the Sham group, the ventricular wall thickened, cardiac function impaired, myocardial fibrosis and inflammatory infiltration became more pronounced, and mRNA and protein expression levels of β-MHC and TGF-β were elevated in the Mod group. In contrast, significant improvements in these indexes were observed in the STP group. Untargeted metabolomics identified 13 differential metabolites and implicated 14 pathways, including arachidonic acid metabolism and the tricarboxylic acid cycle (TCA). Conclusion STP exerts therapeutic effects against HCH and metabolic disorders through multi-target interventions, possibly by regulating energy metabolism and suppressing inflammatory responses.

Key words: Hypertensive Cardiac Hypertrophy, Abdominal Aortic Coarctation, Siwei Tumuxiang Powder, Metabolomics, Rat

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