目的 探讨慢性鼻窦炎伴鼻息肉（CRSwNP）“中医证候-分子机制”关联网络，以及鼻窦炎口服液的干预 机制。方法 通过转录组分析 CRSwNP 相关差异表达基因（DEGs），并将其与中医证候相关基因取交集，得到 CRSwNP 中医证候相关基因，然后进行基因本体论生物学过程（GOBP）和 KEGG 通路富集分析。通过单细胞转 录组分析CRSwNP中医证候相关细胞类型及其标记基因。通过DCABM-TCM、Pubchem、SwissTargetPrediction、 TCMSP和Uniprot数据库得到鼻窦炎口服液的入血成分及潜在作用靶点，将其与CRSwNP相关DEGs取交集，得 到鼻窦炎口服液入血成分治疗CRSwNP的潜在作用靶点，并进一步评估鼻窦炎口服液干预CRSwNP的主要细胞 类型及生物学过程。结果 共鉴定出62个CRSwNP中医证候相关独有基因，其中风热犯肺证12个、脾胃湿热 证19个、脾肺气虚证7个及胆经湿热证24个，分别与凝血及细胞黏附、细胞发育、物质代谢及调节、神经系 统发育及钙离子信号传导等生物学过程及信号通路密切相关。CRSwNP各中医证候相关基因均显著富集在白细 胞介导免疫、淋巴细胞介导免疫、炎症反应调节等炎症免疫相关生物学过程及信号通路。单核巨噬细胞在 CRSwNP风热犯肺证、胆经湿热证、脾胃湿热证等实证的作用评分中最高，B细胞在CRSwNP脾肺气虚证的作 用评分中最高。鉴定出 7个单核巨噬细胞的实证相关标记基因，实证高评分单核巨噬细胞（HM）的细胞通讯及 细胞代谢水平与实证低评分单核巨噬细胞（LM）存在显著差异，HM的吞噬作用、炎症反应、氧化应激、细胞凋 亡活性均高于LM。共得到50个鼻窦炎口服液治疗CRSwNP的潜在作用靶点；鼻窦炎口服液可能主要通过作用 于循环细胞、分泌细胞、基底细胞、浆细胞、单核巨噬细胞等细胞类型来改善CRSwNP；潜在作用靶点主要富 集在氧化应激、慢性炎症反应、上皮细胞增殖调节等相关生物学过程及信号通路。结论 CRSwNP相关风热犯 肺证、胆经湿热证、脾胃湿热证和脾肺气虚证之间存在分子机制异质性；炎症免疫反应在CRSwNP相关中医证 候发生发展过程中发挥重要作用；单核巨噬细胞在CRSwNP实证中扮演重要角色；鼻窦炎口服液通过多组分、 多靶点、多通路协同机制治疗CRSwNP。

Objective To explore the association network of “Traditional Chinese Medicine （TCM）syndromesmolecular mechanism”of chronic rhinosinusitis with nasal polyps（CRSwNP）and the intervention mechanism of Bidouyan Oral Liquid. Methods CRSwNP related differentially expressed genes（DEGs）from the transcriptome analysis were intersected with TCM syndrome related genes to obtain CRSwNP TCM syndrome related genes， which were used to perform Gene Ontology Biological Process（GOBP）and KEGG pathway enrichment analysis. The cell types and marker genes related to TCM syndromes in CRSwNP were explored by single cell transcriptome analysis. The blood-entering components and potential targets of Bidouyan Oral Liquid were obtained from DCABM-TCM， Pubchem， SwissTargetPrediction， TCMSP and Uniprot databases. The potential targets of Bidouyan Oral Liquid in treating CRSwNP were obtained by intersection of potential targets of Bidouyan Oral Liquid with CRSwNP related DEGs，and the main cell types and biological processes of Bidouyan Oral Liquid in treating CRSwNP were further evaluated. Results A total of 62 CRSwNP unique genes were identified， including 12 wind-heat invading lung syndrome， 19 spleenstomach damp-heat syndrome，7 spleen-lung qi deficiency syndrome and 24 gallbladder damp-heat syndrome. They were closely related to multiple biological processes and signal pathways，including coagulation and cell adhesion，cell development，substance metabolism and regulation，nervous system development and calcium ion signal transduction. CRSwNP TCM syndromes related genes were significantly enriched in inflammatory immune related biological processes and signal pathways such as leukocyte mediated immunity， lymphocyte mediated immunity， inflammatory response regulation， etc. Mono/macrophages has the highest function score in CRSwNP wind-heat invading lung syndrome， gallbladder damp-heat syndrome， spleen-stomach damp-heat syndrome， B cell has the highest function score in CRSwNP spleen-lung qi deficiency syndrome. Seven marker genes associated with mono/macrophages were identified. There were significant differences in cell-to-cell communication and metabolism between mono/macrophages with high empirical score（HM）and mono/macrophages with low empirical score（LM）. Phagocytosis， inflammatory response， oxidative stress and apoptosis activity of HM were higher than those of LM. A total of 50 potential targets of Bidouyan Oral Liquid in treating CRSwNP were obtained. Bidouyan Oral Liquid may improve CRSwNP mainly by affecting circulating cells， secretory cells， basal cells， plasma cells， mono/macrophages and other cell types. The potential targets of Bidouyan Oral Liquid in treating CRSwNP are mainly concentrated in biological processes and signal pathways responding to oxidative stress， chronic inflammatory response， epithelial cell proliferation regulation， etc. Conclusion：CRSwNP related wind-heat invading lung syndrome，gallbladder damp-heat syndrome，spleen-stomach damp-heat syndrome and spleen-lung qi deficiency syndrome exhibit molecular mechanism heterogeneity. The inflammatory immune response plays an important role in the occurrence and development of CRSwNP related TCM syndrome. Mono/macrophages play an important role in CRSwNP excess syndrome. Bidouyan Oral Liquid treats CRSwNP through multi-component，multi-target and multi-pathway synergistic mechanism.

R285.5；R857.3

国家自然科学基金项目 （82305325）；广东省基础与应用基础研究基金项目 （2021A1515110446）；广州市科技基础与应用基础研究 项目 （202201011211）；广州市科技计划-市校 （院） 联合资助基础与应用基础研究项目 （2024A03J0046）；李云英全国名老中医药专家传承工 作室建设项目[粤中医办函 （2022） 52号]