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第44卷第1期                           南京医科大学学报(自然科学版)
                  2024年1月                   Journal of Nanjing Medical University(Natural Sciences)     · 1  ·


               ·基础研究·

                A2M 在慢性阻塞性肺疾病中的表达及其与免疫细胞浸润的相

                关性



                肖心儒 ,范 亮 ,施宇佳 ,张 倩             1,2*
                      1
                              1
                                       1
                南京医科大学附属常州市第二人民医院呼吸与危重症医学科,江苏                         常州   213003;南京医科大学常州医学中心,江苏             常
                1                                                                 2
                州 213003


               [摘   要] 目的:研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者外周血α2巨球蛋白(alpha 2 macro⁃
                globulin,A2M)与免疫细胞浸润的相关性。方法:对GSE38974数据集进行综合分析。GO富集、KEGG 分析和GSVA 分析用于
                探索潜在的功能和通路。CIBERSORT用于评估组织浸润性免疫细胞。收集25例稳定期COPD患者和26例健康对照,分析外
                周血A2M水平与免疫细胞计数的相关性。ELISA检测血浆中A2M的浓度。RT⁃qPCR检测细胞和外周血中A2M mRNA的表达
                水平。Western blot法检测M2型巨噬细胞表面标志物精氨酸酶(arginase⁃1,Arg⁃1)的表达水平。采用Pearson相关分析进行相
                关性分析。ROC 曲线判断 A2M 的诊断灵敏度与特异度。结果:对 GSE38974 数据集的差异表达基因进行生物信息学分析发
                现,A2M在COPD患者肺组织中表达下降,且与COPD患者肺组织的免疫细胞浸润相关。RT⁃qPCR和ELISA结果显示,A2M水
                平在COPD患者外周血中下调,与COPD患者淋巴细胞、单核细胞具有相关性。ROC曲线提示A2M具有诊断COPD的价值。进一
                步的通路分析提示A2M可能与巨噬细胞等调节免疫途径相关。在M2巨噬细胞中敲低A2M后Arg⁃1的表达降低。结论:A2M
                在 COPD 患者肺组织与外周血中表达降低,与 COPD 患者免疫细胞计数、免疫细胞浸润等密切相关,A2M 可能在巨噬细胞向
                M2型极化的过程中发挥了重要作用。
               [关键词] 慢性阻塞性肺疾病;α2巨球蛋白;免疫细胞浸润
               [中图分类号] R563                    [文献标志码] A                        [文章编号] 1007⁃4368(2024)01⁃001⁃12
                doi:10.7655/NYDXBNSN230597



                The expression of A2M in chronic obstructive pulmonary disease and its correlation with
                immune cell infiltration

                                     1
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                                               1
                XIAO Xinru ,FAN Liang ,SHI Yujia ,ZHANG Qian 1,2*
                Department of Respiratory and Critical Care Medicine,Affiliated Changzhou NO.2 People’s Hospital of Nanjing
                1
                Medical University,Changzhou 213003;Changzhou Medical Center,Nanjing Medical University,Changzhou
                                                    2
                213003,China
               [Abstract] Objective:To investigate the correlation between peripheral blood alpha 2 macroglobulin(A2M)and immune cell
                infiltration in patients with chronic obstructive pulmonary disease(COPD). Methods:Comprehensive analysis of the GSE38974
                dataset was performed. GO enrichment,KEGG analysis,and GSVA analysis were used to explore potential functions and pathways.
                CIBERSORT was used to assess tissue⁃ infiltrating immune cells. Peripheral blood A2M levels and immune cell counts were analyzed
                in 25 stable COPD patients and 26 healthy controls. ELISA was used to detect the concentration of A2M in plasma. RT⁃qPCR was used
                to measure A2M mRNA expression levels in cells and peripheral blood. Western blot was used to measure the expression levels of the
                M2 macrophage surface marker arginase⁃1(Arg⁃1). Pearson correlation analysis was used for correlation analysis. ROC curve was used
                to determine the diagnostic sensitivity and specificity of A2M. Results:Bioinformatics analysis of differentially expressed genes in
                GSE38974 dataset revealed that A2M expression was decreased in lung tissue of COPD patients and was correlated with immune cell

               [基金项目] 江苏省社会发展项目(BE2020651);江苏省第五期“333”高层次人才项目(BRA2020015);常州市高层次医学人
                才项目(2022CZLJ013);南京医科大学常州医学中心科研项目(CMCB202214)
                ∗
                通信作者(Corresponding author),E⁃mail:qianzhang@njmu.edu.cn
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