中国药物警戒 ›› 2026, Vol. 23 ›› Issue (7): 767-774.
DOI: 10.19803/j.1672-8629.20250886

• 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

基于转录组学探究四味土木香散对大鼠高血压性心肌肥厚的作用机制

魏明慧1, 刘芳冰2, 李祥名3, 李健英3, 张佳茹2, 尹东杰3, 任中杰3, 郭颖3, 王敏杰3, 薛明明3,*   

  1. 1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 010100;
    2内蒙古医科大学第二附属医院,内蒙古 呼和浩特 010100;
    3内蒙古医科大学基础医学院,内蒙古 呼和浩特 010100
  • 收稿日期:2025-12-07 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:魏明慧,女,硕士,助理实验师,心血管生理学。
  • 基金资助:
    国家自然科学基金资助项目（82360095）; 内蒙古自治区自然科学基金资助项目（2022LHMS08002）; 内蒙古自治区科技计划项目（2020GG0238）; 内蒙古医科大学面上项目（YKD2023MS041）; 内蒙古自治区自然科学基金资助项目（2020MS08139）; 内蒙古自治区高等学校创新团队发展计划（NMGIRT2420）

Mechanisms of action of Siwei Tumuxiang powder against hypertensive myocardial hypertrophy in rats based on transcriptomics

Wei Minghui1, Liu Fangbing2, Li Xiangming3, Li Jianying3, Zhang Jiaru2, Yin Dongjie3, Ren Zhongjie3, Guo Ying3, Wang Minjie3, Xue Mingming3,*   

  1. 1Laboratory and Experimental Equipment Management Center of Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China;
    2The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China;
    3School of Basic Medical Sciences of Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China
  • Received:2025-12-07 Online:2026-07-15 Published:2026-07-16

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摘要： 目的 探究四味土木香散改善高血压性心肌肥厚的作用机制,为临床治疗高血压性心肌肥厚提供参考。方法 通过对大鼠腹主动脉进行结扎建立心肌肥厚模型,结合转录组学技术和RT-qPCR等方法进行探究。将18只SD大鼠随机分为假手术（Sham）组、模型（Mod）组、四味土木香散给药（STP）组（1.6 g·kg-1·d-1）,每组各6只,Mod、STP组通过腹主动脉缩窄术构建高血压性心肌肥厚模型,STP组给予四味土木香散溶液灌胃,Sham组和Mod组以等体积生理盐水灌胃。喂养8周后,采用超声心动图评价各组大鼠心功能;取心肌组织病理切片进行苏木精-伊红（HE）、Masson染色,观察心肌组织病理结构的改变及心肌纤维化的程度;基于Western Blot技术检测肥厚相关蛋白;经过网络药理学模拟,构建成分-靶点网络图并进行通路富集分析,预测四味土木香散治疗高血压性心肌肥厚的潜在生物途径。利用RNA-Seq技术进行测序,分析差异基因,并对差异基因进行GO、KEGG富集分析,通过qPCR验证目标基因的表达。结果 超声心动图结果显示STP组大鼠左室前壁厚度（AWT）、左室后壁厚度（PWT）显著降低,射血分数（EF）、左室短轴缩短率（FS）显著升高;HE、Masson染色结果显示,四味土木香散干预可改善高血压性心肌肥厚大鼠的心肌组织病理学改变,包括减轻心肌细胞排列紊乱与细胞肥大程度、减少炎症细胞浸润,并明显缩小心肌血管周围及组织间隙的胶原纤维沉积区域;Western Blot结果显示四味土木香散可以降低肥厚相关蛋白ANP、细胞纤维化相关蛋白COL-1的表达;网络药理学结果显示四味土木香散中的150个主要成分可能通过124个潜在核心靶点发挥治疗高血压性心肌肥厚的作用;转录组测序结果显示Sham组与Mod组共有1 168个差异基因,Mod组与STP组之间共有47个差异基因,交集有22个回调基因,其中3个基因（Hamp、Ndrg1、Gfpt2）与高血压性心肌肥厚相关。RT-qPCR结果显示四味土木香散可以逆转Hamp、Ndrg1、Gfpt2等基因在高血压性心肌肥厚模型大鼠心脏组织中的表达。结论 四味土木香散通过补体和凝血级联反应、PPAR信号通路、胆固醇代谢等通路调控Hamp、Ndrg1、Gfpt2等基因来改善高血压性心肌肥厚的发生发展。

关键词: 高血压性心肌肥厚, 四味土木香散, 转录组学, 补体和凝血级联反应, PPAR信号通路, 胆固醇代谢, 大鼠

Abstract: Objective To investigate the mechanism by which Siwei Tumuxiang powder ameliorates hypertensive myocardial hypertrophy so as to provide a reference for clinical treatment. Methods A rat model of myocardial hypertrophy was established via abdominal aortic ligation. Transcriptomics technology and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used. Eighteen Sprague-Dawley (SD) rats were randomly divided into three groups: the sham-operated group (Sham), the model group (Mod), and the Siwei Tumuxiang powder administration group (STP, 1.6 g·kg-1·d-1), with six rats in each. A model of hypertensive myocardial hypertrophy was constructed via abdominal aortic coarctation in the Mod and STP groups. The STP group was given STP solution by gavage at a dose of 1.6 g·kg-1·d-1, while the Sham and Mod groups received an equal volume of normal saline by gavage. After 8 weeks of feeding, echocardiography was used to evaluate the cardiac function of each group. Heart tissue sections were stained with HE and Masson to observe the pathological changes in the structure of myocardial tissue and the degree of myocardial fibrosis. Western blot was used to detect the expressions of hypertrophy-related proteins. Based on network pharmacology simulation, a component-target network map was constructed and pathway enrichment analysis was conducted to predict the potential biological pathways of Siwei Tumuxiang powder against hypertensive myocardial hypertrophy. RNA-Seq was used for sequencing to analyze the differentially expressed genes, which were subjected to GO and KEGG enrichment analysis. The expressions of target genes were verified by qPCR. Results Echocardiography showed that the AWT and PWT of the STP group were significantly reduced, while EF and FS were significantly increased. HE and Masson staining suggested that Siwei Tumuxiang powder could mitigate the disordered arrangement of myocardial cells, cell hypertrophy, inflammatory infiltration, and the appearance of obvious fibrotic areas around myocardial vessels and in myocardial tissue spaces. Western blot showed that the expressions of hypertrophy-related protein ANP and fibrosis-related protein COL-1 were inhibited. The results of network pharmacology indicated that the 150 main components in Siwei Tumuxiang powder might exert therapeutic effects against hypertensive myocardial hypertrophy through 124 potential core targets. RNA-Seq identified 1 168 differentially expressed genes between the Sham group and the Mod group, and another 47 between the Mod group and the STP group. There were 22 feedback expressed genes in the intersection, among which 3 differentially expressed genes were related to hypertensive myocardial hypertrophy: Hamp, Ndrg1, and Gfpt2. RT-qPCR showed that Siwei Tumuxiang powder could reverse the expressions of Hamp, Ndrg1, and Gfpt2 genes in the heart tissue of model rats of hypertensive myocardial hypertrophy. Conclusions iwei Tumuxiang powder can retard the occurrence and development of hypertensive myocardial hypertrophy by regulating Hamp, Ndrg1, and Gfpt2 genes through complement and coagulation cascade, PPAR signaling pathway, and cholesterol metabolism pathways.

Key words: Hypertensive Myocardial Hypertrophy, Siwei Tumuxiang Powder, Transcriptomics, Coagulation Cascade, PPAR Signaling Pathway, Cholesterol Metabolism Pathways, Rats

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