陈与丰 陈建新 王雅蕾

摘要 目的：通过网络药理学方法探讨泽泻汤治疗梅尼埃病（Meniere Disease，MD）的作用机制。方法：利用SymMap、TCMSP、TCMID、BATMAN-TCM等中医药数据库及TargetNet药物-靶点谱在线计算平台，获取泽泻汤有效成分及作用靶点;通过OMIM、Gene Cards、TTD、CTD等疾病基因数据库，获取MD相关靶标基因;利用STRING蛋白质数据库，构建蛋白质-蛋白质相互作用（PPI）网络;利用Cytoscape信息分析软件，获取关键靶标基因、构建中药-有效成分-靶标基因网络图;利用R软件进行信号通路分析。结果：泽泻汤中69种有效成分可作用于88个MD相关基因，以核受体（如糖皮质激素受体）为主要作用靶点，参与IL-17、肿瘤坏死因子（TNF）相关的核因子κB信号通路介导的炎症反应。结论：由核受体糖皮质激素受体-核因子κB介导的炎症反应通路，可能是泽泻汤减少MD炎症反应，缓解膜迷路水肿的重要作用途径之一。

关键词 梅尼埃病;糖皮质激素受体;泽泻汤;网络药理学;炎症反应

Abstract Objective：To explore the mechanism of Zexie Decoction in the treatment of Meniere disease（MD） based on network pharmacology.Methods：SymMap，TCMSP，TCMID，BATMAN-TCM and other Chinese medicine databases and TargetNet drug-target spectrum online computing platform were used to obtain the effective ingredients and targets of Zexie Decoction; through OMIM，Gene Cards，TTD，CTD and other disease gene databases，MD-related target genes were obtained; STRING protein database were used to construct a protein interaction network; Cytoscape information analysis software was used to obtain key target genes，a network diagram of traditional Chinese medicine-active ingredients-target genes was constructed; R software was used to analyze signal pathways.Results：A total of 69 active components were screened from Zexie Decoction.These components acted on 88 related targets of MD.It took nuclear receptors （such as glucocorticoid receptors） as the main targets，and participated in the inflammatory response mediated by IL-17 and TNF-related NFκB signaling pathways.Conclusion：The inflammatory response pathway mediated by the nuclear receptor glucocorticoid receptor-NFκB may be one of the important pathways for Zexie Decoction to reduce MD inflammatory response and relieve membrane labyrinth edema.

Keywords Meniere Disease; Glucocorticoid receptor; Zexie Decoction; Network pharmacology; Inflammation

中圖分类号：R289.5;R276文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.07.008

梅尼埃病（Meniere Disease，MD）是一种病因复杂、发病机制尚不明确的内耳疾病，以自发性的发作性眩晕、感音神经性耳聋（Sensorineural Hearing Loss，SNHL）、耳鸣和耳胀闷感为主要临床表现，膜迷路积水为主要病理学特征[1]。流行病学研究显示，MD在全球范围内均有发生，10万人中有3.5～513人患病，近10年来发病率呈上升趋势[2-3]。MD高发年龄为40～60岁，且患病率随年龄增长而增加，发病时常表现为单侧耳症状，并可持续数十年，每年发作6～11次[3]。近50%的MD患者合并抑郁症，78%～89%的MD患者正常工作、生活受到限制，严重影响生命质量[4-6]。尽管MD发病机制尚不明确，但研究普遍认为，膜迷路积水是其主要病理机制之一。……