基于网络药理学和实验验证探讨附子治疗变应性鼻炎的作用机制研究

Study on the mechanism of Fuzi in the treatment of allergic rhinitis based on network pharmacology and experimental validation

目的:研究附子治疗变应性鼻炎(allergic rhinitis,AR)的关键作用靶点基因和信号通路。方法:使用TCMPS和PubChem数据库,用口服生物利用度和药物相似度作为筛选条件筛选出附子的活性成分及作用靶点基因,使用GeneCards数据库筛选出AR的靶点基因。利用在线工具Venny2.1筛选出附子治疗AR的作用靶点基因;利用STRING数据库获取药物疾病作用靶点的蛋白互作(Protein-protein interaction,PPI)网络,通过MCC算法找出关键靶点基因。通过GO富集和KEGG富集分析找到潜在的生物学过程和信号通路。最后,进行了动物实验证明附子对AR的治疗作用。结果:使用TCMSP、PubChem和GeneCards数据库筛选出附子中21种活性化合物成分和附子对AR的潜在治疗靶点基因68个。PPI网络分析找出前十个关键靶点基因,分别为:PTGS2、TNF、IL6、AKT1、ALB、STAT3、CCL2、CXCL8、VEGFA和JUN。GO功能和KEGG通路富集分析显示附子对AR的作用靶点显著富集的功能和通路与AR密切相关。最后通过动物实验验证附子对AR的治疗是有效的。结论:AR患者鼻黏膜组织中IL-6和TNF-α的表达增加,与变应性鼻炎疾病活动相关指标呈正相关。附子通过抑制小鼠鼻黏膜中Toll样信号通路的活化,降低IL-6和TNF-α的表达活性,从而改善了AR小鼠的炎症改变。

Objective:To study the key target genes and signaling pathways in the treatment of allergic rhinitis(AR)with radix aconiti lateralis preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the active ingredi⁃ents and target genes of Fuzi using oral bioavailability and drug similarity as screening conditions,and the GeneCards database was used to screen the target genes of AR.The online tool Venny2.1 was used to screen the target genes of Fuzi for the treatment of Allergic Rhinitis;the STRING database was used to obtain the protein⁃protein interaction(PPI)network of drug⁃disease targets,and the key target genes were identified by the MCC algorithm.The potential biological processes and signaling pathways were identified by GO enrichment and KEGG enrichment analysis.Finally,animal experiments were conducted to demonstrate the ther⁃apeutic effect of Fuzi on allergic rhinitis.Results:The TCMSP,PubChem and GeneCards databases were used to screen the 21 active compound components of Fuzi and 68 potential therapeutic target genes of Fuzi for Allergic Rhinitis.PPI network analysis identified the top ten key target genes,namely:PTGS2,TNF,IL6,AKT1,ALB,STAT3,CCL2,CXCL8,VEGFA and JUN.GO functional and KEGG pathway enrichment analysis showed that the significantly enriched functions and pathways of Fuzi on allergic rhinitis were closely related to allergic rhinitis.Finally,animal experiments were conducted to verify that Fuzi is effec⁃tive in the treatment of allergic rhinitis.Conclusion:Increased expression of IL⁃6 and TNF⁃αin nasal mucosal tissues of patients with allergic rhinitis was positively correlated with indicators related to the disease activity of allergic rhinitis.Fuzi ameliorated the inflammatory changes in mice with allergic rhinitis by inhibiting the activation of toll⁃like signaling pathway in the nasal mucosa and decreasing the expression activity of IL⁃6 and TNF⁃α.