Effect and Mechanism of M-CSF on Cardiac Function after Acute Myocardial Infarction in Mice by Regulating Cardiac Macrophages
10.11969/j.issn.1673-548X.2024.08.009
- VernacularTitle:M-CSF调控心脏巨噬细胞对小鼠急性心肌梗死后心功能的影响及机制研究
- Author:
Shudi ZHANG
1
;
Qingyan ZHAO
;
Zhibin PENG
Author Information
1. 430060 武汉大学人民医院、武汉大学心血管病研究所、心血管病湖北省重点实验室
- Keywords:
Macrophages;
Myocardial infarction;
Myocardial injury;
Cardiac function;
Structural remodeling
- From:
Journal of Medical Research
2024;53(8):42-47
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of macrophage colony stimulating factor(M-CSF)on myocardial function after acute myocardial infarction(AMI)in mice by regulating cardiac macrophages.Methods Fifty C57mice were randomly di-vided into Sham Group(n=10,sham operation group),MI Group(n=20,AMI model was prepared,and normal saline was injected in-traderitoneally)and MM Group { n=20,AMI model was prepared,and M-CSF reagent[500μg/(kg·d)]was injected intraderitoneal-ly}.At the end of the experiment,after completing a cardiac ultrasound,the myocardial tissue was collected,interleukin-4(IL-4),interleukin-6(IL-6),monocyte ehemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),interferon-α(IFN-α),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),Collagen Ⅰ and Collagen Ⅲ were detected by enzyme-linked immunosorbent assay(ELISA),the apoptosis-related proteins Bax,C-caspase-3,caspase-3,nuclear transcription facter(NF)-κB p65,transduction and activator of transcription 3(STAT3),transduction and activator of transcription 6(STAT6)were detected by Western blot assay,and the neovascularization markers in MI peripheral area were determined by immunohis-tochemistry,the expression levels of M1-type macrophages and M2-type macrophages were detected by flow cytometry.Results The left ventricular size and left ventricular ejection fraction(LVEF)were significantly improved in MM Group when compared with the MI Group,and the indexex of myocardial inflammation,hypertrophy,apoptosis,and fibrosis decreased significantly(P＜0.05).The expres-sion of neovascularization mardker CD31 was significantly up-regulated in MM Group.The expression of M2macrophage in MM group was significantly higher than when compared with the MI group,while the level of M1 macrophage was lower(P＜0.05).The expression of NF-κB p65 in MI group was statistically higher than that in the Sham group and MM group,while the levels of STAT3 and STAT6 were higher in the MM group than in the MI group(P＜0.05).Conclusion M-CSF can inhibit inflammatory response,reduce myo-cardial fibrosis,hypertrophy and apoptosis,promote angiogenesis,inhibit M1-type macrophages and up-regulate the expression of M2-type macrophages to promote myocardial tissue repair and improve ventricular structural remodeling,in which NF-κB/STAT signa-ling pathway plays an important role.
