机构地区:[1]西南医科大学附属医院呼吸与危重症医学科,泸州646000 [2]成都医学院第一附属医院呼吸与危重症医学科,成都610500
出 处:《国际呼吸杂志》2023年第11期1290-1302,共13页International Journal of Respiration
摘 要:目的:通过分析特发性肺纤维化(IPF)患者肺组织的单细胞转录组测序(scRNA-seq)数据,联合芪白平肺胶囊的网络药理学,探索IPF患者中与芪白平肺胶囊调控相关的免疫细胞、靶基因及其潜在机制。方法:从基因表达综合数据库(GEO)下载IPF患者(IPF组)和正常者(对照组)的scRNA-seq数据,采用随机数字表法在2组中各选取20个样本用于分析IPF的免疫细胞群及其比例变化。对各免疫细胞群进行差异基因分析,将P<0.05和|logFC|>0.6的基因鉴定为差异基因。对差异基因进行基因本体论(GO)-生物过程富集分析,探索参与IPF疾病进程的潜在分子功能及机制。基于中药系统药理学数据库与分析平台(TCMSP)获取芪白平肺胶囊主要活性成分和靶基因,并对靶基因进行GO和京都基因与基因组百科全书(KEGG)富集分析。通过将芪白平肺胶囊靶基因映射到IPF免疫细胞差异基因,构建"活性成分-靶基因-免疫细胞"网络。通过GO和KEGG富集分析探索芪白平肺胶囊用于治疗IPF患者的潜在作用机制。通过STRING数据库和Cytoscape软件对"活性成分-靶基因-免疫细胞"网络中靶基因进行蛋白质互作分析并寻找关键靶基因。结果:在IPF组和对照组的肺组织中共发现B细胞、T细胞和先天淋巴细胞等18个免疫细胞群。与对照组比较,IPF组中经典2型树突状细胞、肥大细胞、浆细胞样树突细胞和调节性T细胞比例均增加,差异均有统计学意义(均P<0.05)。18个免疫细胞群共包含534个差异基因,参与了淋巴细胞的活化、抗原的加工和呈递、白细胞的迁移和趋化作用等免疫相关生物过程。芪白平肺胶囊包含18个有效活性成分和239个靶基因,其中联苯双酯、槲皮素、毛异黄酮等9个活性成分靶向IPF中除浆细胞样树突细胞外的17个免疫细胞群与IL-1B、VEGFA、FOS等42个差异基因。这些靶向差异基因主要富集于活性氧或氧化应激相关通路与多个免疫�Objective To explore the potential mechanisms of the Qibai Pingfei Capsule on immune cells and target genes in idiopathic pulmonary fibrosis(IPF)patients by analyzing single cell RNA sequencing(scRNA-seq)data from lung tissues of IPF patients,combined with the network pharmacology of Qibai Pingfei Capsule.Methods The scRNA-seq data of lung tissues in IPF patients(IPF group)and normal individuals(control group)were first downloaded from the Gene Expression Omnibus(GEO).Twenty samples were randomly selected from each group using the random number table method to explore the immune cell population and its proportion changes in IPF.Differential gene analysis was conducted on each immune cell population,and genes with P<0.05 and|log Fold Changes(logFC)|>0.6 were identified as differentially expressed genes.Gene Ontology(GO)-biological process enrichment analysis on differentially expressed genes was performed to explore the potential molecular functions and mechanisms involved in the progression of IPF.The primary active molecules and target genes of Qibai Pingfei Capsule were obtained based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and GO and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on target genes.The"active molecules-target genes-immune cells"network was constructed by mapping the target genes of Qibai Pingfei Capsule to differentially expressed genes of IPF immune cells.The GO and KEGG enrichment analysis were conducted to explore the potential mechanism of Qibai Pingfei Capsule in the treatment of IPF.Protein-protein interaction(PPI)analysis was conducted by the Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape software to understand the interaction relationship of target genes in the"active molecules-target genes-immune cells"network and to identify key target genes.Results The scRNA-seq analysis revealed a total of 18 immune cell populations in IPF lung tissues,including B cells,T cells,and
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