基于液相色谱-质谱的心肌梗死急性期小鼠磷酸化修饰蛋白质组学分析

高旸; 张建; 胡世钰; 王婧璞; 王羿文; 曹嘉添; 张峰

doi:10.12025/j.issn.1008-6358.2025.20250210

基于液相色谱-质谱的心肌梗死急性期小鼠磷酸化修饰蛋白质组学分析

LC-MS-based phosphoproteomic profiling of the acute phase of myocardial infarction in mice

摘要

摘要:
目的探讨心肌梗死（myocardial infarction，MI）急性期小鼠心肌蛋白质磷酸化修饰的变化。
方法将8周的C57BL/6J小鼠6只随机均分为两组，分别进行MI造模或假手术。造模72 h后提取小鼠心肌组织蛋白样品。通过液相色谱-质谱联合（liquid chromatograph-mass spectrometer，LC-MS）分析技术检测MI组与假手术组的小鼠心肌组织的蛋白质磷酸化修饰，并对结果进行差异修饰蛋白分析、富集分析、聚类分析以及蛋白质互作分析。
结果 LC-MS分析共发现了1 921个差异磷酸化修饰位点（包含20个酪氨酸磷酸化位点和1 901个丝氨酸/苏氨酸磷酸化位点）和851种存在差异磷酸化修饰的蛋白质。其中，与假手术组相比，MI组中有1 545个位点的磷酸化修饰明显上调，376个位点的磷酸化修饰下调（P＜0.05）。
结论本研究通过LC-MS分析筛选出小鼠MI后急性期心肌表达水平存在显著差异的磷酸化位点和蛋白质，为分组机制探究和治疗靶点开发提供参考。

Abstract:
Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice.
Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network.
Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05).
Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

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