中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (25): 6544-6553.doi: 10.12307/2026.471

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

蛋白质组学和代谢组学联合应用分析冠心病模型小鼠的病理机制

刘瑾薇1，张  丹2，郭红丽2，陈  欢2，李晶晶2，曹纬国1   

  1. 1重庆医科大学中医药学院，重庆市   400016；2重庆中医药学院中药学院，重庆市   402760
  • 收稿日期:2025-10-15 修回日期:2026-03-05 出版日期:2026-09-08 发布日期:2026-04-22
  • 通讯作者: 曹纬国，硕士，教授，博士生导师，重庆医科大学中医药学院，重庆市 400016 通讯作者：李晶晶，博士，副研究员，重庆中医药学院中药学院，重庆市 402760
  • 作者简介:刘瑾薇，女，2000年生，江西省上饶市人，汉族，重庆医科大学在读硕士，主要从事中药药理心血管方面研究。
  • 基金资助:
    国家自然科学基金(82304770)，项目负责人：李晶晶；重庆市博士后特别资助(2023CQBSHTB2014)，项目负责人：李晶晶；重庆市自然科学基金面上项目(CSTB2024NSCQ-MSX0697)，项目负责人：李晶晶；重庆市自然科学基金面上项目(CSTB2022NSCQ-MSX1553)，项目负责人：郭红丽；重庆市教委科学技术研究项目(KJQN202215132)，项目负责人：陈欢

Combined proteomics and metabolomics analysis of pathological mechanisms in mouse models of coronary heart disease

Liu Jinwei1, Zhang Dan2, Guo Hongli2, Chen Huan2, Li Jingjing2, Cao Weiguo1   

  1. 1College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China; 2College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China
  • Received:2025-10-15 Revised:2026-03-05 Online:2026-09-08 Published:2026-04-22
  • Contact: Cao Weiguo, MS, Professor, Doctoral supervisor, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China Co-corresponding author: Li Jingjing, PhD, Associate researcher, College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China
  • About author:Liu Jinwei, MS candidate, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
  • Supported by:
    National Natural Science Foundation of China, No. 82304770 (to LJJ); Chongqing Postdoctoral Special Funding, No. 2023CQBSHTB2014 (to LJJ); Chongqing Natural Science Foundation (General Program), Nos. CSTB2024NSCQ-MSX0697 (to LJJ) and CSTB2022NSCQ-MSX1553 (to GHL); Science and Technology Research Program of Chongqing Education Commission, No. KJQN202215132 (to CH)

PDF

1

摘要：


文题释义：
蛋白质组学：能够全面捕捉生物体内蛋白质的表达谱、修饰状态及相互作用网络，揭示疾病发生发展过程中关键蛋白的调控机制。
代谢组学：可精准检测生物体液或组织中内源性代谢物的变化，反映机体代谢网络的动态失衡。

背景：冠心病的发病机制复杂，单一组学方法在理解疾病复杂的生物学途径方面存在局限性，而多组学方法可以从不同水平揭示分子间的相互作用网络，克服单一组学方法的局限性。
目的：通过蛋白质组学和代谢组学探究冠心病模型小鼠的病理机制。
方法：选取健康SPF级8周龄雄性C57BL/6小鼠作为实验动物，随机分为假手术组和模型组。通过结扎冠状动脉左前降支建立冠心病小鼠模型，假手术组仅穿线不结扎。28 d后用心动超声检测小鼠心功能，用TTC染色心脏组织，采用超高效液相色谱-串联质谱技术筛选组间差异蛋白质和代谢物并进行联合组学分析。
结果与结论：①与假手术组相比，模型组小鼠心功能降低，左室射血分数与左室短轴缩短率显著下降(P < 0.05)，心肌梗死面积显著增加  (P < 0.01)；②蛋白质组学结果显示有420个差异蛋白质，其中Serum amyloid A protein、protein kinase D等282个蛋白表达上调，Protein YIPF5、E3 ubiquitin-protein ligase等138个蛋白表达下调；KEGG通路数据库富集显示，其主要涉及ATP依赖性染色质重塑、肾素-血管紧张素系统等通路；③代谢组学结果显示有155个差异代谢物，其中Thromboxane、Tromethamine等56个代谢物上调，N-Acetyl-D-Tryptophan、D-Xylulose 5-Phosphate等99个代谢物下调；KEGG分析显示其与嘌呤代谢途径、甘油磷脂代谢途径相关；④联合分析发现26个差异蛋白质与16个差异代谢物存在相关性，其中涉及ATP1A3、Hexokinase等蛋白以及Cytochalasin B、Gluconasturtiin等代谢物。结论：冠心病发生发展的病理机制与能量代谢网络紊乱、炎症-凝血级联反应激活以及离子稳态调控失衡密切相关。                                               
https://orcid.org/0009-0009-1296-0547 (刘瑾薇) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 蛋白质组学, 代谢组学, 冠心病, 血瘀证, 生物学基础

Abstract: BACKGROUND: The pathogenesis of coronary heart disease is complex. A single omics approach is limited in elucidating its biological pathways, whereas multi-omics integration helps reveal molecular interaction networks across different levels, addressing the limitations of single-omics methods.
OBJECTIVE: To investigate the pathological mechanisms of coronary heart disease in a mouse model using proteomics and metabolomics.
METHODS: Healthy SPF-grade 8-week-old male C57BL/6 mice were randomly divided into a sham operation group and a model group. The mouse model of coronary heart disease was established by ligation of the left anterior descending coronary artery, while the sham operation group underwent threading without ligation. At 28 days post-surgery, cardiac function was assessed by echocardiography, and myocardial infarct size was evaluated by TTC staining. Ultra-high-performance liquid chromatography-tandem mass spectrometry was employed to screen differentially expressed proteins and metabolites between groups for integrated omics analysis.
RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the model group exhibited significantly decreased cardiac function, with reduced left ventricular ejection fraction and fractional shortening (P < 0.05), and a significantly increased myocardial infarction area (P < 0.01). (2) Proteomics identified 420 differentially expressed proteins, including 282 upregulated (e.g., Serum amyloid A protein, protein kinase D) and 138 downregulated (e.g., Protein YIPF5, E3 ubiquitin-protein ligase). Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these proteins were mainly involved in ATP-dependent chromatin remodeling and the renin-angiotensin system. (3) Metabolomics identified 155 differential metabolites, with 56 upregulated (e.g., Thromboxane, Tromethamine) and 99 downregulated (e.g., N-Acetyl-D-Tryptophan, D-Xylulose 5-Phosphate). Kyoto Encyclopedia of Genes and Genomes analysis indicate the association between these metabolites and purine metabolism and glycerophospholipid metabolism pathways. (4) Integrated analysis revealed significant correlations between 26 differentially expressed proteins and 16 differential metabolites, involving proteins such as ATP1A3 and Hexokinase, and metabolites such as Cytochalasin B and Gluconasturtiin. To conclude, these findings suggest that the pathogenesis of coronary heart disease may be closely related to disturbances in energy metabolism networks, activation of inflammation-coagulation cascades, and imbalances in ion homeostasis regulation.

Key words: proteomics, metabolomics, coronary heart disease, blood stasis syndrome, biological basis

中图分类号: