基于网络药理学研究苓桂术甘汤治疗梅尼埃病的作用机制及实验验证  

Study on the mechanism and experimental validation of Linggui Zhugan Decoction in treating Meniere’s disease based on network pharmacology

作　　者：张琦[1] 冷辉[1] 金婧 李明晔 Zhang QI;Leng Hui;Jin Jing;Li Mingye(Affiliated Hospital of Liaoning University of traditional Chinese Medicine Liaoning,ShenYang,110000;Liaoning University of traditional Chinese Medicine Liaoning,ShenYang,110000,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳110000 [2]辽宁中医药大学,辽宁沈阳110000

出　　处：《中国医学文摘（耳鼻咽喉科学）》2024年第1期139-143,16,共6页Chinese Medical Digest(Otorhinolaryngology)

基　　金：吴阶平基金(项目编号:320.6750.18332);辽宁中医药大学附属医院“育苗工程”项目(项目编号:YM202030);辽宁省“百千万人才工程”资助项目(项目编号:辽人社[2018]47);辽宁省科学技术计划(2023JH2/10130055)。

摘　　要：目的本研究通过网络药理学及实验验证的方法对苓桂术甘汤治疗梅尼埃病的作用机制进行探讨。方法使用SymMap和TCMSP数据库检索苓桂术甘汤的主要活性成分及靶点;利用GeneCards和OMIM数据库检索梅尼埃病的靶点;绘制VENN图;将交集提交至STRING数据库,构建蛋白相互作用网络图,并通过Cytoscape3.9.0进行聚类分析,获取苓桂术甘汤治疗梅尼埃病核心靶点;利用Matescape平台对核心靶点靶点进行GO及KEGG分析。实验验证部分:以醋酸去氨加压素诱导梅尼埃病豚鼠模型,检测P38MAPK、p-P38MAPK、ATF-2蛋白在模型组、苓桂组、苓桂+α-LA组的表达,研究苓桂术甘汤对动物模型耳蜗组织MAPK信号通路的影响。结果苓桂术甘汤有效活性成分380个,靶点1975个,梅尼埃病靶点444个,苓桂术甘汤改善梅尼埃病的潜在靶点有89个。EGFR、TNF、IL6、INS、PTEN等可能是苓桂术甘汤治疗梅尼埃病的关键靶点。MAPK通路等可能是苓桂术甘汤治疗梅尼埃病的关键通路。实验验证结果表明,梅尼埃病模型豚鼠较空白组P38MAPK、p-P38MAPK、ATF-2蛋白的表达下调(p<0.01);苓桂术甘汤能使梅尼埃病模型豚鼠上述蛋白的表达上调(p<0.01)。结论MAPK通路是苓桂术甘汤治疗梅尼埃病的关键通路。苓桂术甘汤治疗梅尼埃病具有多成分、多靶点、多通路的特点,为临床开发利用提供基础。Objective This study explored the mechanism of Linggui Zhugan Decoction in the treatment of Meniere’s disease through the methods of network pharmacology and experimental verification.Methods Symmap and tcmsp databases were used to search the main active components and targets of Linggui Zhugan decoction.The targets of Meniere’s disease were retrieved using genecards and OMIM databases.Draw Venn diagram.The intersection was submitted to the string database,and the protein interaction network map was constructed.Through the cluster analysis of Cytoscape 3.9.0,the core target of Linggui Zhugan Decoction in treating Meniere’s disease was obtained.Go and KEGG analysis were performed on the core targets using the matescape platform.Experimental validation:the guinea pig model of Meniere’s disease was induced by desmopressin acetate,and p38MAPK,P-P38MAPK and ATF-2 proteins were detected in the model group,Linggui group and Linggui group+α-Expression of La group.To study the effect of Linggui Zhugan Decoction on MAPK signal pathway in cochlear tissue of animal model.Results Linggui Zhugan decoction has 380 active ingredients and 1975 targets.There were 444 targets of Meniere’s disease,and 89 potential targets of Linggui Zhugan Decoction to improve Meniere’s disease.EGFR,TNF,IL6,ins and PTEN may be the key targets of Linggui Zhugan Decoction in treating Meniere’s disease.MAPK pathway may be the key pathway of Linggui Zhugan Decoction in treating Meniere’s disease.The experimental results showed that the expression of p38MAPK,P-P38MAPK and ATF-2 protein in Meniere’s disease model guinea pigs was lower than that in the blank group(P<0.01);Linggui Zhugan decoction could up regulate the expression of the above proteins in guinea pigs with Meniere disease(P<0.01).Conclusion MAPK pathway is the key pathway of Linggui Zhugan Decoction in the treatment of Meniere’s disease.Linggui Zhugan decoction has the characteristics of multi-component,multi-target and multi-channel in the treatment of Meniere’s diseas

关 键 词：梅尼埃病 苓桂术甘汤 网络药理学 MAPK信号通路 膜迷路积水 耳蜗 

分 类 号：R73[医药卫生—肿瘤]