摘要
目的:通过网络药理学方法探讨中药“萆薢、土茯苓”药对治疗痛风性关节炎的作用机制。方法:首先利用TCMSP中药系统药理学数据库与分析平台,定义生物利用度(OB)≥30%、类药性(DL)≥0.18,寻找目标中药的有效成分和基因靶点,然后通过OMIM、DisGeNET、GeneCards数据库,挖掘痛风性关节炎疾病相关的基因靶点。最后对两种基因取交集,构建中药--成分--靶基因--疾病的中药调控网络,对网络里面的基因构建蛋白互作网络,找到核心基因,进行GO和KEGG的分析。结果:中药萆薢、土茯苓的有效成分总共84个,筛选后获得有效成分17个,基因靶点180个。确定痛风性关节炎的疾病靶点600个,二者共同靶点基因58个,PPI网络分析发现IL-1β、VEGFA、MAPK1、IL-10、PTGS2可能是“萆薢、土茯苓”药对治疗痛风性关节炎的关键靶点。GO富集分析确定了1399个条目(P<0.05),其中生物过程主要包括生物刺激、生物调节、细胞代谢等;KEGG通路富集分析明确了152条信号通路,其中信号通路涉及炎症、代谢、衰老等方面,主要包括IL-4信号通路、IL-10信号通路、IL-13信号通路、IL-17信号通路等。结论:“萆薢、土茯苓”药对通过多靶点、多通路作用于痛风性关节炎,主要起到抗炎免疫的作用,降尿酸、保肝肾机制尚未明确,需要借助分子生物学研究,完善“萆薢、土茯苓”药对的作用机制,为临床用药组方提供新思路。
Objective The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)≥30%and drug-likeness(DL)≥0.18.Also,databases including OMIM,DisGeNET,GeneCards were utilized to mine genetic targets related to gouty arthritis disease.Finally,the two genes were intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network were used to construct a protein interaction network to find core genes for analysis of GO and KEGG.ResultsThere were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,of which 17 effective ingredients and 180 genetic targets were obtained after screening.Totally 600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL-1β,VEGFA,MAPK1,IL-10,and PTGS2 may be Key targets for treating gouty arthritis..GO enrichment analysis identified 1399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,aging mainly including the IL-4,IL-10,IL-13,IL-17signal pathway etc.Conclusion"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.
作者
白子兴
曹旭含
孙承颐
杨艳军
孙卫东
董永丽
魏戌
杨丽平
BAI Zi-xing;CAO Xu-han;SUN Cheng-yi;YANG Yan-jun;SUN Wei-dong;DONG Yong-li;WEI xu;YANG Li-ping(Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing,100102,China;Beijing University of Chinese Medicine,Beijing,100029,China)
出处
《海南医学院学报》
CAS
2020年第8期611-617,共7页
Journal of Hainan Medical University
基金
国家中医药管理局基地专项(JDZX2015277)
北京市科学技术委员会科技新星项目(Z191100001119025)。
关键词
萆薢
土茯苓
痛风性关节炎
网络药理学
作用机制
Bi xie
Tu fuling
Gouty arthritis
Network pharmacology
Mechanism of action
