病理性心肌重构小鼠模型的构建及转录组测序分析

doi:10.16352/j.issn.1001-6325.2026.10.1322

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (10): 1322-1328.doi: 10.16352/j.issn.1001-6325.2026.10.1322

病理性心肌重构小鼠模型的构建及转录组测序分析

刘如意¹, 邓慧², 张姝³, 杨晓雯¹, 董大千¹, 刘天龙¹, 郑巍^4*

内蒙古医科大学附属医院 1.药学部; 2.神经内科;3. 耳鼻喉科,内蒙古呼和浩特 010059;
4.内蒙古扎兰屯市中蒙医院药剂科,内蒙古呼伦贝尔 162650

收稿日期:2025-08-29 修回日期:2026-04-08 出版日期:2026-10-05 发布日期:2026-09-18
通讯作者: ^*149893235@qq.com
基金资助:
内蒙古自治区医师协会临床医学研究和临床新技术推广项目(YSXH2024KYF049);内蒙古医科大学青年培育项目(YKD2021QN013);内蒙古医科大学教育教学改革研究与实践项目(NYJXGGSJ2024024);内蒙古医科大学附属医院博士启动金计划(NYFYBS202132)

Construction of a murine model of pathological cardiac remodeling and transcriptomic analysis

LIU Ruyi¹, DENG Hui², ZHANG Shu³, YANG Xiaowen¹, DONG Daqian¹, LIU Tianlong¹, ZHENG Wei^4*

1. Department of Pharmacy; 2. Department of Neurology; 3. Department of Otolaryngology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059;
4. Department of Pharmacy, the Zhalantun Traditional Chinese and Mongolia Medicine Hospital, Hulunbuir 162650, China

Received:2025-08-29 Revised:2026-04-08 Online:2026-10-05 Published:2026-09-18
Contact: ^*149893235@qq.com

摘要/Abstract

摘要： 目的通过对小鼠心肌转录组测序数据分析,筛选对病理性心肌重构形成具有调控作用的转录因子。方法通过皮下植入血管紧张素Ⅱ(AngⅡ)微渗透泵的方式构建病理性心肌重构小鼠模型并对模型进行评价,心肌组织转录组测序并分析,筛选组间表达差异的转录因子,通过基因集富集分析(GSEA)富集与心肌重构发生相关的信号通路,利用皮尔森相关分析明确转录因子与信号通路的相关性并验证。结果 AngⅡ微渗透泵植入4周后,心脏的结构和功能发生明显改变,与对照组小鼠相比,模型组小鼠左心室的收缩功能显著降低,表现为模型组小鼠左室射血分数(EF)和缩短分数(FS)明显降低(P＜0.05),且模型组小鼠的心重比和心胫比显著增加(P＜0.05)。心肌组织麦胚凝集素染色和天狼猩红染色结果显示,模型组小鼠的心肌细胞表面积与纤维化程度较正常小鼠显著增加(P＜0.05)。对转录组测序数据进行分析发现,转录因子Etv4在模型小鼠心肌组织中表达显著增加,细胞外基质(ECM)受体相互作用通路在模型组小鼠心肌组织中被显著活化,且Etv4在心肌组织中的表达与ECM受体通路中的基因表达呈显著正相关(P＜0.05),这也在蛋白水平被验证。结论 Etv4可能通过调控ECM受体通路促进病理性心肌重构的形成,为该病新型治疗药物的开发提供新的靶点。

关键词: 转录因子Etv4, 细胞外基质受体相互作用通路, 病理性心肌重构

Abstract: Objective Mouse myocardial transcriptome sequencing data were analyzed to identify transcription factors regulating pathological cardiac remodeling,and to elucidate its mechanism. Methods A mouse cardiac remodeling model was established via subcutaneous implantation of angiotensin Ⅱ(AngⅡ) micro-osmotic pump,and the mouse model was evaluated at anatomical and pathological levels.Transcriptomic sequencing of mouse myocardial tissue was performed to identify differentially expressed transcription factors between groups.Gene Set Enrichment Analysis(GSEA) was employed to delineate relevant signalling pathways.Pearson correlation analysis was used to establish correlations between transcription factors and signalling pathways,which were validated by western blot. Results After micro-osmosis pump implantation for 4 weeks,significant alterations in cardiac structure and function were observed. Compared with control mice,the mice in model group exhibited markedly reduced ejection fraction(EF) and shortening fraction(FS)(P＜0.05),while heart-to-tibia weight ratio and heart-to-leg ratio were significantly increased in the model group mice(P＜0.05).The myocardial WGA staining and Picro Sirius Red staining of myocardial tissue revealed that the mouse heart in model group exhibited significant increased in cardiac hypertrophy and fibrosis(P＜0.05).Transcriptomic sequencing data revealed a significantly increase in transcription factor Etv4 expression in mouse myocardial tissue from the model mice compared with vehicle mice. The extracellular matrix(ECM) receptor pathway was markedly activated,and Etv4 expression in myocardial tissue showed a significant positive correlation with gene expression involved in the ECM receptor pathway(P＜0.05),which was further validated at the protein level. Conclusions The transcription factors Etv4 may facilitate pathological cardiac remodeling, potentially via the ECM receptor pathway.

Key words: transcription factor Etv4, extracellular matrix receptor interaction pathway, pathological myocardial remodelling

中图分类号:

刘如意, 邓慧, 张姝, 杨晓雯, 董大千, 刘天龙, 郑巍. 病理性心肌重构小鼠模型的构建及转录组测序分析[J]. 基础医学与临床, 2026, 46(10): 1322-1328.

LIU Ruyi, DENG Hui, ZHANG Shu, YANG Xiaowen, DONG Daqian, LIU Tianlong, ZHENG Wei. Construction of a murine model of pathological cardiac remodeling and transcriptomic analysis[J]. Basic & Clinical Medicine, 2026, 46(10): 1322-1328.

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病理性心肌重构小鼠模型的构建及转录组测序分析

Construction of a murine model of pathological cardiac remodeling and transcriptomic analysis

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