摘要目的:对良性气道狭窄（BAS）患者肉芽组织成纤维细胞进行蛋白质组学分析，以进一步揭示BAS的发病机制。方法:取5例BAS患者的肉芽组织（BAS组）和3例肺癌患者的正常支气管组织（对照组）进行成纤维细胞原代培养，用同位素标记相对和绝对定量（iTRAQ）技术分析成纤维细胞的蛋白质组表达情况，筛选差异表达蛋白，并使用基因本体（GO）数据库、京都基因和基因组（KEGG）数据库和重复出现邻近基因检索工具（STRING）数据库对差异表达蛋白的功能、代谢通路和蛋白相互关系进行富集分析。结果:共筛选出93个差异表达蛋白。其中有36个差异表达蛋白在BAS肉芽组织成纤维细胞中显著下调，57个差异表达蛋白显著上调。差异表达蛋白主要定位于细胞膜和细胞外区域，参与离子结合功能、代谢活性功能，主要参与的通路有糖酵解-糖异生代谢、细胞外基质-受体结合、磷脂酰肌醇3-激酶（PI3K）-AKT信号传导、复杂环境中的微生物代谢和次级代谢物合成。结论:BAS狭窄部位肉芽组织成纤维细胞的细胞外基质-受体结合异常、PI3K-AKT信号通路异常和代谢异常可能与BAS的发生发展有关。

abstractsObjective:To perform the proteomics profiles of fibroblasts in granulation tissue from patients with benign airway stenosis (BAS) and thereby investigate the pathogenesis of BAS.Methods:Granulation tissue from 5 patients with BAS (BAS group) and normal bronchial tissue from 3 patients with lung cancer (control group) were harvested for primary culture of fibroblasts. The profile of proteome expression was examined with isobaric tags for relative and absolute quantitation (iTRAQ) to screen for differentially expressed proteins (DEPs) . The Gene Ontology (GO) database, Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Search Tool for Recurring Instances of Neighboring Genes (STRING) database were used for enrichment analysis of the functions, metabolic pathways and interactions of the differentially expressed proteins.Results:A total of 93 DEPs were screened, among them, 36 were significantly down-regulated, and 57 were significantly up-regulated, in fibroblasts of granulation tissue of BAS. The DEPs were mainly localized on cell membrane and in the extracellular domain, and were engaged in ion binding and metabolic activity. The major pathways involved were glycolysis-gluconeogenesis metabolism, extracellular matrix-receptor binding, phosphatidylinositol 3-kinase (PI3K) -AKT signaling, microbial metabolism and secondary metabolite synthesis in complex environments.Conclusion:Abnormalities in extracellular matrix-receptor binding, PI3K-AKT signaling pathway and metabolism in fibroblasts of granulation tissue in lesion of BAS may be related to occurrence and development of BAS.