Arginine Metabolic Disorder in Heart Failure Rats： Analysis Based on Targeted Metabolomics and Bioinformatics

LI Zeyu; WANG Xiaoqing; FANG Zhengyu; ZHAO Yurou; XIAO He; LIU Penghaobang; ZHANG Haiming; LIU Chunyan; HU Yanhong

doi:10.13422/j.cnki.syfjx.20260444

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Arginine Metabolic Disorder in Heart Failure Rats： Analysis Based on Targeted Metabolomics and Bioinformatics

更新时间：2026-04-28

- Arginine Metabolic Disorder in Heart Failure Rats： Analysis Based on Targeted Metabolomics and Bioinformatics
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 10, Pages: 229-237(2026)
- 作者机构：
  
  中国中医科学院医学实验中心，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20260444
  CLC： R277;R285;R289
- Received：15 January 2026，
  
  Revised：2026-03-02，
  
  Accepted：04 March 2026，
  
  Online First：10 March 2026，
  
  Published：20 May 2026
- 稿件说明：
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李泽宇,王晓晴,房政钰等.基于靶向代谢组学和生物信息学分析心力衰竭大鼠精氨酸代谢失调[J].中国实验方剂学杂志,2026,32(10):229-237.

LI Zeyu,WANG Xiaoqing,FANG Zhengyu,et al.Arginine Metabolic Disorder in Heart Failure Rats： Analysis Based on Targeted Metabolomics and Bioinformatics[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(10):229-237.
李泽宇,王晓晴,房政钰等.基于靶向代谢组学和生物信息学分析心力衰竭大鼠精氨酸代谢失调[J].中国实验方剂学杂志,2026,32(10):229-237. DOI： 10.13422/j.cnki.syfjx.20260444.

LI Zeyu,WANG Xiaoqing,FANG Zhengyu,et al.Arginine Metabolic Disorder in Heart Failure Rats： Analysis Based on Targeted Metabolomics and Bioinformatics[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(10):229-237. DOI： 10.13422/j.cnki.syfjx.20260444.

摘要

目的

该研究系统分析心力衰竭大鼠模型中的精氨酸代谢失调，为阐释心力衰竭病机提供现代科学依据，并为中医药防治提供新思路。

方法

通过开胸手术结扎大鼠左冠状动脉前降支，造成心肌急性缺血，从而诱导心肌梗死后心力衰竭的形成，分为假手术组和模型组，每组8只。运用超高效液相色谱-三重四极杆质谱（UPLC-TQ-S）技术进行血清靶向代谢组学分析，并利用空气动力辅助解吸电喷雾电离质谱成像（AFADESI-MSI）技术观察心脏组织中代谢物的空间分布。通过人类基因综合数据库（GeneCards）、基因表达综合数据库（GEO）等筛选心力衰竭与精氨酸代谢相关靶点，构建蛋白质-蛋白质相互作用（PPI）网络，并进行京都基因与基因组百科全书（KEGG）通路、基因本体（GO）富集分析。对核心代谢成分与关键靶点进行分子对接验证，并基于核心通路及靶标进行中药预测。

结果

与假手术组比较，模型组大鼠血清中精氨酸、瓜氨酸水平显著下降（

0.01），脯氨酸、鸟氨酸、肌酸、肌酐及谷氨酸水平明显升高（

0.05，

0.01）。心脏质谱成像显示，心肌局部精氨酸丰度下降。生物信息学分析筛选出24个核心作用靶点，如血管紧张素转换酶（ACE）、神经型一氧化氮合酶1（NOS1）、5-羟色胺2A受体（HTR2A）、表皮生长因子受体（EGFR）等，富集分析提示其显著参与钙信号通路、神经活性配体-受体相互作用及磷脂酰肌醇信号通路。分子对接证实，精氨酸、瓜氨酸与HTR2A，肌酸、肌酐与EGFR等具有较强结合活性。基于通路靶点预测出人参、厚朴等潜在干预中药。

结论

该研究揭示了心力衰竭状态下存在特征性的精氨酸代谢紊乱，其核心靶点与磷脂酰肌醇信号通路密切相关，从代谢物与信号通路层面为心力衰竭的中医病机提供了现代生物学诠释，为心力衰竭的靶向治疗及中医药开发提供借鉴。

Abstract

Objective

This study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）.

Methods

A thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets.

Results

Compared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （

0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （

0.05，

0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified.

Conclusion

This study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

关键词

Keywords

references

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