基于网络药理学的羌活-益智仁药对联合糖皮质激素治疗肾病综合征机制研究  

Study on Mechanism of Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus Medicinal Pair Combined with Glucocorticoid for Nephrotic Syndrome Based on Network Pharmacological Approach

作　　者：顾浩[1] 王娟 韩森 李立[1] 赵宁[1] 傅强[3] 崔赵丽[4] 丁治国[4] 王光磊[3] 姜淼[1] GU Hao;WANG Juan;HAN Sen;LI Li;ZHAO Ning;FU Qiang;CUI Zhaoli;DING Zhiguo;WANG Guanglei;JIANG Miao(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Weifang Traditional Chinese Medicine Hospital,Weifang 262699,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;East District of Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101100,China)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]潍坊市中医院,山东潍坊262699 [3]北京中医药大学东直门医院,北京100700 [4]北京中医药大学东直门医院东区,北京101100

出　　处：《中国中医药信息杂志》2021年第3期27-32,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81873181、81473367);国家自然科学基金青年基金(81603401);中央级公益性科研院所基本科研业务费专项资金(Z0659、Z0647);北京市科技计划(Z121100000312006)。

摘　　要：目的利用网络药理学方法研究羌活-益智仁辅助糖皮质激素治疗肾病综合征(NS)的作用机制。方法通过TCMSP、TCMID、Stitch、Uniprot数据库收集羌活、益智仁的活性成分和靶点,应用GeneCards、OMIM、NCBI-gene、Malacard数据库检索NS靶点,利用GeneCards、NCBI-gene、OMIM数据库查找糖皮质激素治疗靶点,分析得到三者的异同靶点。将NS靶点输入String数据库获得蛋白相互作用网络,通过DAVID数据库进行KEGG通路富集分析,并利用Cytoscape3.7.2软件进行可视化,将羌活-益智仁药对与糖皮质激素的药理网络与NS疾病网络进行比对分析。结果筛选出羌活活性成分15种,益智仁活性成分4种,谷甾醇为两药共有成分。获得羌活靶点基因83个,益智仁靶点基因51个,NS疾病基因1229个,糖皮质激素靶点基因2695个,羌活-益智仁药对与糖皮质激素共同作用于NS的靶点有26个。基于NS疾病网络发现了20个疾病核心模块,羌活-益智仁药对涉及其中70%核心模块。KEGG通路富集分析得到羌活相关通路65条、益智仁相关通路26条、NS相关通路106条,羌活-益智仁药对与NS直接相关的通路共33条,糖皮质激素同样作用于这些通路。结论羌活-益智仁药对可能通过作用于REAL、TNF-α、CASP8等靶点,以及PI3K-Akt、HIF-1、雌激素等相关通路,增强糖皮质激素对NS的治疗作用,并通过调节NF-κB通路、脂肪的消化吸收和细胞色素P450通路减少糖皮质激素抵抗和股骨头坏死等不良反应。Objective To study the mechanism of Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus medicinal pair combined with glucocorticoid for nephrotic syndrome(NS)based on network pharmacological approach.Methods Active ingredients and targets of Notopterygii Rhizoma et Radix and Alpiniae Oxyphyllae Fructus were explored through TCMSP,TCMID,Stitch and Uniprot database.The NS targets were explored through GeneCards,OMIM,NCBI-gene and Malacard database.The targets of glucocorticoid were explored through GeneCards,NCBI-gene and OMIM database.The similarities and differences of the three targets were analyzed.The NS targets were input into String database to obtain the protein interaction network.KEGG pathway enrichment analysis was performed through the DAVID database.Cytoscape 3.7.2 software was used for visualization.The pharmacological network of Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus medicinal pair and glucocorticoid were compared with NS disease network and analyzed.Results 15 active ingredients of Notopterygii Rhizoma et Radix and 4 active ingredients of Alpiniae Oxyphyllae Fructus were screened out.Sitosterol was a common ingredient of the two drugs.83 target genes of Notopterygii Rhizoma et Radix,51 target genes of Alpiniae Oxyphyllae Fructus,1229 NS disease genes,and 2695 glucocorticoid target genes were obtained.26 targets of Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus medicinal pair combined with glucocorticoid acted on NS targets together.Based on the NS disease network,20 disease core modules were discovered,and Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus medicinal pair involved 70%of the core modules.KEGG pathway enrichment analysis revealed 65 Notopterygii Rhizoma et Radix-related pathways,26 Alpiniae Oxyphyllae Fructus-related pathways,and 106 NS-related pathways.Notopterygii Rhizoma et Radix-Alpiniae Oxyphyllae Fructus medicinal pair had 33 pathways directly related to NS.Glucocorticoid could also act on these pathways.Conclusion Notopterygii Rhizoma e

关 键 词：肾病综合征 羌活 益智仁 糖皮质激素 网络药理学 

分 类 号：R272.969.2[医药卫生—中医儿科学] R285[医药卫生—中医学]