Quercitrin promotes M2 macrophage polarization after myocardial infarction in mice through the JAK2/STAT3 signaling pathway

doi:10.3969/j.issn.1009-976X.2025.05.004

Abstract

Abstract: Objective To investigate the effects of quercitrin on ventricular remodeling after myocardial infarction in mice and its underlying mechanisms,providing a basis for the application of quercitrin in cardiovascular diseases. Methods In the in vivo experiment,a mouse model of myocardial infarction was established. Single-cell RNA sequencing technology was used to analyze the immune cell and macrophage subtypes in the myocardial tissue of mice treated with quercitrin. In the in vitro experiment, mouse bone marrow macrophages were isolated and cultured. The polarization state of macrophages was detected after treatment with quercitrin. Western Blot and qPCR were used to detect the protein and gene expression of the JAK2/STAT3 signaling pathway,and the role of the pathway was verified using the JAK inhibitor Ruxolitinib. Results In the in vivo experiment, single-cell RNA sequencing revealed that quercitrin altered the composition of immune cells in the myocardium of mice with myocardial infarction. The total proportion of macrophages increased, with an increase in M2-type macrophage subtypes（such as Macro_Chil1, Macro_Cd163）and a decrease in M1-type（such as Macro_Cd86）. In the in vitro experiment, flow cytometry showed that quercitrin increased the proportion of M2-type macrophages（P<0.05）and decreased M1-type（P<0.01）. Western Blot and qPCR results indicated that the expression of TGF-β1,TGF-β2, VEGF-A,and VEGF-B in mouse macrophages was upregulated after quercitrin treatment（all P<0.001）, and this upregulation was reversed by the JAK inhibitor Ruxolitinib. Conclusion Quercitrin promotes M2 macrophage polarization by activating the JAK2/STAT3 signaling pathway,inhibits inflammatory responses,and promotes angiogenesis,thereby improving ventricular remodeling after myocardial infarction.

Key words: myocardial infarction, ventricular remodeling, quercitrin, macrophages, single-cell sequencing

摘要： 目的探讨槲皮苷对小鼠心肌梗死后心室重构的影响及作用机制,为槲皮苷在心血管疾病中的应用提供依据。方法体内实验部分,通过构建小鼠心肌梗死模型,利用单细胞RNA测序技术,对槲皮苷处理后的小鼠心肌组织免疫细胞和巨噬细胞亚群类型进行分析。体外实验部分,分离培养小鼠骨髓巨噬细胞,用槲皮苷处理后检测巨噬细胞极化状态,通过Western blot和qPCR检测JAK2/STAT3信号通路相关蛋白和基因的表达,用JAK抑制剂Ruxolitinib验证通路作用。结果体内实验中,单细胞RNA测序结果显示,槲皮苷改变了心肌梗死小鼠心肌组织中免疫细胞的组成：总巨噬细胞比例增加,且巨噬细胞亚群分布呈现M2型（如Macro_Chil1、Macro_Cd163）增多、M1型（如Macro_Cd86）减少的特征。体外实验中,流式细胞分析显示槲皮苷使M2型巨噬细胞比例上升（P<0.05）,M1型下降（P<0.01）;Western blot和qPCR结果显示槲皮苷处理后小鼠巨噬细胞TGF-β1、TGF-β2、VEGF-A和VEGF-B的表达上调（P<0.001）,JAK抑制剂Ruxolitinib可逆转这种表达上调。结论槲皮苷通过激活JAK2/STAT3信号通路促进M2型巨噬细胞极化,从而抑制炎症反应并促进血管生成,最终改善心肌梗死后心室重构。

关键词: 心肌梗死, 心室重构, 槲皮苷, 巨噬细胞, 单细胞测序

CLC Number:

R654.2

LIU Cong-yong, FU Yuan, LI Jing-wen, CENG Hui, ZHENG Jun-meng, GAO Min-nan. Quercitrin promotes M2 macrophage polarization after myocardial infarction in mice through the JAK2/STAT3 signaling pathway[J]. Lingnan Modern Clinics In Surgery, 2025, 25(05): 302-311.

刘丛勇, 傅媛, 李婧雯, 曾晖, 郑俊猛, 高敏楠. 槲皮苷通过JAK2/STAT3信号通路促进小鼠心肌梗死后M2型巨噬细胞极化[J]. 岭南现代临床外科, 2025, 25(05): 302-311.

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