白细胞介素-10过表达巨噬细胞的极化和靶向成像研究  

Investigation on the polarization and targeting imaging of macrophages overexpressing interleukin-10

作　　者：王铭仪 程洋 蔡星璇 陈捷 周珊珊 张硌 陈韵岱 WANG Mingyi;CHENG Yang;CAI Xingxuan;CHEN Jie;ZHOU Shanshan;ZHANG Luo;CHEN Yundai(Medical School of Chinese PLA,Beijing 100853,China;Senior Department of Cardiology,the Sixth Medical Center of PLA General Hospital,Beijing 100048,China;Department of Cardiology,First Medical Center of PLA General Hospital,Beijing 100853,China;The Second Medical School of Southern Medical University,Guangzhou 510515,China;The Medical Innovation Research Division of PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军医学院,北京100853 [2]中国人民解放军总医院第六医学中心心血管病医学部,北京100048 [3]中国人民解放军总医院第一医学中心心血管内科,北京100853 [4]南方医科大学第二临床医学院,广东广州510515 [5]中国人民解放军总医院医学创新研究部,北京100853

出　　处：《分子影像学杂志》2024年第5期451-457,共7页Journal of Molecular Imaging

基　　金：国家自然科学基金(32371490)。

摘　　要：目的通过转录组测序和离体组织成像技术探讨过表达白细胞介素(IL)-10对巨噬细胞极化和动脉粥样硬化(AS)斑块靶向能力的潜在影响。方法通过慢病毒感染构建过表达IL-10的巨噬细胞(IL-10M),进行转录组测序与差异基因分析,通过RT-qPCR和流式细胞术验证巨噬细胞极化标志物的表达变化。通过尾静脉注射,将IL-10M和ConM注入西方饮食造模后的ApoE-/-小鼠,利用主动脉大体和病理荧光成像观察细胞对主动脉斑块的靶向能力。结果转录组分析显示,IL-10M与对照组(ConM)有1271个差异表达基因,其中与巨噬细胞极化相关的多个关键基因差异显著。IL-10M中,M1型标志物Cd86、肿瘤坏死因子(Tnf)表达下调,Il-1beta表达上调;M2型标志物甘露糖受体1(Mrc1)表达上调,精氨酸酶2(Arg2)表达下调。RT-qPCR验证发现IL-10M Mrc1、Tnf-alpha和Il-1beta表达与测序结果一致。流式分析结果显示,与ConM相比,IL-10M组中CD86表达水平较低(P<0.05)。尾静脉注射后,小鼠主动脉斑块处可分别观察到IL-10M和ConM的荧光信号。结论过表达IL-10可调节巨噬细胞极化相关标志物的表达,并且可以不改变巨噬细胞对斑块的靶向能力。Objective To comprehensively investigate the potential impact of interleukin-10(IL-10)overexpression on macrophage polarization and their targeting capabilities towards atherosclerotic plaques through transcriptome sequencing and ex vivo tissue imaging techniques.Methods Transcriptome sequencing and differential gene analysis were performed after infecting macrophages with a lentivirus to induce overexpression of IL-10(IL-10M).The changes in expression levels of macrophage polarization markers were validated using RT-qPCR and flow cytometry.Subsequently,ApoE-/-mice were intravenously administered IL-10M and ConM via the tail vein after being fed a Western diet,and the targeting efficiency of cells towards aortic plaques was assessed through ex vivo and histological fluorescence imaging.Results Transcriptomic analysis revealed that there were 1271 differentially expressed genes in IL-10M compared to the control group(ConM).The IL 10M group exhibited significant expression changes in several key genes associated with macrophage polarization.M1 phenotype markers Cd86 and tumor necrosis factor(Tnf)exhibited downregulation,while Il-1beta demonstrated upregulation in IL-10M;M2 phenotype marker mannose receptor 1(Mrc1)displayed upregulation,whereas arginase-2(Arg2)showed downregulation.RT-qPCR confirmed the expression of Mrc1,Tnf-alpha,and Il-1beta in IL-10M,consistent with the sequencing results.Furthermore,flow cytometry revealed a reduction in CD86 expression levels in IL-10M compared to ConM.After intravenous injection,fluorescence signals of IL-10M and ConM can be respectively observed at the site of atherosclerotic plaque in mice aorta.Conclusion The overexpression of IL-10 modulated the expression of markers associated with macrophage polarization while preserving their targeting ability towards plaques.This discovery establishes a scientific foundation for further investigation into the potential role of IL-10 in preventing and treating atherosclerosis,thereby supporting the development of novel anti-inflammator

关 键 词：白细胞介素-10 巨噬细胞 极化 靶向 动脉粥样硬化 

分 类 号：R54[医药卫生—心血管疾病]