基于网络药理学探讨芦根对慢性支气管炎的影响及作用机制

Effect of Rhizoma Phragmitis on Chronic Bronchitis Based on Network Pharmacology and Its Mechanism

目的:根据网络药理学对中药芦根治疗慢性支气管炎的活性成分以及潜在的作用机制进行研究。方法:通过Traditional Chinese Medicine Systems Pharmacology(TCMSP)、Traditional Chinese Medicine Integrated Database(TCMID)数据库检索芦根的活性成分,采用SwissTargetPrediction以及Similarity ensemble approach (SEA)数据库检索活性成分对应的靶点。使用Therapeutic Target Database(TTD)、Genetic Association Database (GAD)数据库检索慢性支气管炎的靶点,UniProt数据库对靶点进行标准化处理。使用String数据库构建靶点相互作用网络。通过Cytoscape3.2.1中的CluoGO插件对芦根作用靶点进行GO分类富集分析,借助KOBAS 3.0对芦根的作用靶点进行KEGG通路富集分析,Cytoscape3.2.1软件构建芦根化学成分、靶点、通路等相关的网络图。采用LPS诱导的支气管上皮细胞炎症模型,给予芦根水煎液处理,检测IL-6、TNF-α水平以及Ptgs2、Nr3c1、Mapk14 mRNA表达。结果:获得芦根8个活性成分,相对应的靶点378个,慢性支气管炎的靶点186个;芦根治疗慢性支气管炎的潜在靶点23个包括IL-6、TNF、MAPK14等;富集分析得到GO条目共43个,其中GO-BP条目17个,GO-CC条目11个,GO-MF条目15个,KEGG富集分析得到139条通路。芦根水煎液可能通过影响AGE-RAGE信号通路的相关靶点IL-6、TNF-α、PTGS2、NR3C1、MAPK14达到治疗慢性支气管炎的效果。结论:本研究初步说明芦根对于治疗慢性支气管炎的药理作用机制,对于后续的深层研究提供了一定的基础。

Objective:To study the active ingredients and possible mechanisms of Rhizoma Phragmitis in the treatment of chronic bronchitis based on network pharmacology. Methods:To retrieve active ingredients of Rhizoma Phragmitis through Chinese Medicine System Pharmacology Database(TCMSP) and Chinese Medicine Comprehensive Database. The Swiss Target Prediction database and the SEA database were used to retrieve and collect targets of active ingredients. The targets of chronic bronchitis were retrieved and collected through TTD and GAD database, and the targets were processed with the UniProt database. The String database was used to construct the protein interaction network. The CluoGO was used to perform GO classification and enrichment analysis of Rhizoma Phragmitis action targets, and KOBAS 3.0 was used to perform the KEGG pathway enrichment analysis of Rhizoma Phragmitis action targets. The networks of chemical composition, target, pathway and other related map of Rhizoma Phragmitis were established by Cytoscape 3.2.1 Software. The inflammatory model of Human bronchial epithelial cells induced by LPS was used, and the model cells were treated with Rhizoma Phragmites decoction, the levels of IL-6,TNF-α and the mRNA expression of Ptgs2,Nr3 c1 and Mapk14 were detected. Results:Eight active components of Rhizoma Phragmitis were obtained, and 378 targets of these active components, 186 chronic bronchitis related targets were obtained. 23 potential targets of Rhizoma Phragmitis for chronic bronchitis were observed, including IL-6、TNF、MAPK14. The enrichment analysis obtained 43 GO entries, including 17 GO-BP entries, 11 GO-CC entries, and 15 GO-MF entries. 139 pathways were analyzed in KEGG enrichment analysis. Rhizoma Phragmitis treated chronic bronchitis through AGE-RAGEsignal pathway related targets ALOX5,CHRM1,MAPK14,P2 RX7,SLC6 A4, etc. Conclusion:The pharmacological mechanism of Rhizoma Phragmitis in the treatment of chronic bronchitis is initially explained, and it provides a certain basis for further in-depth research.