基于网络药理学原理探讨健脾补肾方治疗肌萎缩侧索硬化症的机制  

Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology

作　　者：林佳成 郑煊璐 王呈蕙 潘卫东[2] LIN Jiacheng;ZHENG Xuanlu;WANG Chenghui;PAN Weidong(Central Laboratory,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Encephalopathy,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院中心实验室,上海201203 [2]上海中医药大学附属曙光医院脑病科,上海201203

出　　处：《上海中医药大学学报》2022年第S01期180-186,共7页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81373619)

摘　　要：目的:本研究通过网络药理学的研究方法,从分子机制和物质基础的角度探讨健脾补肾方的作用机制。方法:利用疾病数据库与中药数据库获取健脾补肾方治疗肌萎缩侧索硬化症(ALS)的潜在靶点,利用DAVID数据库进行京都基因与基因组百科全书(KEGG)通路和基因本体(GO)富集分析,利用String数据库建立蛋白-蛋白互相作用(PPI)网络,利用Cytoscape软件建立和分析靶点网络。结果:KEGG富集结果提示健脾补肾方治疗ALS的机制可能涉及对细胞存活(磷脂酰肌醇3-激酶/蛋白激酶B通路,PI3K/Akt通路)、炎症(丝裂原活化蛋白激酶通路,MAPKs通路)、钙离子信号通路的调控。GO分析结果提示健脾补肾方主要调控细胞凋亡、蛋白磷酸化、蛋白结合等过程。PPI网络提示其主要调控的蛋白家族为谷氨酸离子型受体家族、MAPKs、半胱氨酸蛋白酶家族。靶点网络分析提示其调控的主要靶点为细胞凋亡相关基因,包括半胱氨酸蛋白酶3(CASP3)、胱抑素C(CYCS)、肿瘤蛋白53(TP53)。健脾补肾方的主要有效成分可能是槲皮素、木犀草素、山柰酚等。结论:健脾补肾方可能通过多途径抑制神经元死亡和神经炎症治疗ALS。Objective:This study aims to explore the molecular mechanism and material basis of Jianpi Bushen Decoction via network pharmacology.Methods:Potential targets of Jianpi Bushen Decoction on amyotrophic lateral sclerosis(ALS)were obtained by disease database and traditional Chinese medicine database.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Ontology(GO)enrichment analysis were performed using DAVID database.The protein-protein interaction(PPI)network was constructed using String database.And target network was analyzed and established by Cytoscape software.Results:KEGG enrichment analysis showed that the mechanism of Jianpi Bushen Decoction on ALS may involve the cell survival(phosphatidylinositol 3-kinase/protein kinase B pathway,PI3K/Akt pathway),inflammation(mitogen-activated protein kinase pathway,MAPKs signaling),and calcium signaling pathway.GO enrichment analysis showed that Jianpi Bushen Decoction could regulate apoptosis,protein phosphorylation,protein binding and other processes.PPI network showed that glutamate ionic receptor family,MAPKs,and cysteine aspirate protease family were the main protein family.Target network analysis suggested that the main regulatory targets were apoptosis related genes,including cysteine protease 3(CASP3),cystatin C(CYCS)and tumor protein 53(TP53).Quercetin,luteolin,and kaempferol may be the potential active ingredients of Jianpi Bushen Decoction.Conclusion:Jianpi Bushen Decoction may treat ALS by inhibiting neuronal death and neuroinflammation through multiple pathways.

关 键 词：健脾补肾方 肌萎缩侧索硬化症 网络药理学 谷氨酸受体 

分 类 号：R285[医药卫生—中药学]