摘要
目的探讨巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF)通过调控心脏巨噬细胞对小鼠急性心肌梗死(acute myocardial infarction,AMI)后心功能的影响及机制。方法50只C57小鼠随机分为Sham组(n=10,制备假手术组)、MI组(n=20,制备AMI模型,随后予以腹腔注射0.9%氯化钠溶液)和MM组{n=20,制备AMI模型,随后予以腹腔注射M-CSF试剂[500μg/(kg·d)]}。实验结束时行心脏超声检查,采集心肌组织,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测白细胞介素-4(interleukin-4,IL-4)、白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化蛋白-1(monocyte ehemoattractant protein-1,MCP-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-10(interleukin-10,IL-10)、干扰素-α(interferon-α,IFN-α)、心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、Collagen Ⅰ及Collagen Ⅲ;Western blot法检测凋亡蛋白Bax、C-caspase-3、caspase-3及核转录因子(nuclear transcription facter,NF)-κB p65、信号转导与转录激活因子3(transduction and activator of transcription 3,STAT3)、信号转导与转录激活因子6(transduction and activator of transcription 6,STAT6)等;免疫组化法测定AMI周边区新生血管标志物;流式细胞术测定M1型、M2型巨噬细胞水平。结果与MI组比较,MM组小鼠左心室大小明显改善,左心室射血分数(left ventricular ejection fraction,LVEF)明显增加,心肌炎症、肥大、凋亡及纤维化指标均明显下降,MM组新生血管标志物CD31水平较MI组表达明显上调。MM组小鼠M2型巨噬细胞水平明显高于MI组,但M1型巨噬细胞水平低于MI组(P<0.05)。MI组小鼠NF-κB p65水平较Sham组与MM组明显升高,且MM组STAT3与STAT6水平显著高于MI组(P<0.05)。结论M-CSF可明显抑制炎性反应,减轻心肌纤维化、肥大及凋亡,促进血管新生,抑制M1型巨噬细胞,上调表达M2型巨噬细胞,促进心肌组织修复,改善�
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 divided into Sham Group(n=10,sham operation group),MI Group(n=20,AMI model was prepared,and normal saline was injected intraderitoneally)and MM Group{n=20,AMI model was prepared,and M-CSF reagent[500μg/(kg·d)]was injected intraderitoneally}.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 immunohistochemistry,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 expression 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 M1macrophage 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
作者
张淑娣
赵庆彦
彭芝斌
曹真
柯元甲
付韫韬
张淑娟
ZHANG Shudi;ZHAO Qingyan;PENG Zhibin(Renmin Hospital of Wuhan University,Cardiovascular Research Insititute,Wuhan University,Hubei Key Laboratory of Cardiology,Hubei 430060,China)
出处
《医学研究杂志》
2024年第8期42-47,共6页
Journal of Medical Research
基金
国家自然科学基金资助项目(面上项目)(81970277)
中央高校基本科研业务费专项资金资助项目(2042022kf1111)。
关键词
巨噬细胞
心肌梗死
心肌损伤
心功能
结构重构
Macrophages
Myocardial infarction
Myocardial injury
Cardiac function
Structural remodeling
