基于网络药理学预测中药复方治疗骨关节炎的分子机制

Prediction on Molecular Mechanism of Chinese Compound Recipes in the Treatment of Osteoarthritis Based on Network Pharmacology

目的:探索骨关节炎(OA)治疗中药的核心配伍及其可能作用机制。方法:检索中国生物医学文献数据库中治疗OA的中药复方,采用Access 2003建立药物数据库,运用复杂网络方法建立药物配伍网络,以网络相对中心度较高的前5味药作为治疗OA的核心配伍。查找中药主要有效成分的人类活性靶蛋白和OA相关基因,采用通路分析软件(IPA)分析平台对中药及OA分子网络进行整合分析。结果:共纳入复方208首,牛膝、当归、甘草、杜仲和白芍构成核心配伍;去重后的靶蛋白共97个,OA相关基因365个。相关度评分较高的OA和中药分子网络功能均涉及结缔组织、骨骼和肌肉疾病、炎症和代谢性疾病。网络整合分析显示:TP53、PTPN1、RELA、DNMT1、NFκB1和VDR是OA和中药分子网络共同直接作用的分子;OA基因相关经典通路中,与中药靶蛋白相关度较高的通路有28条细胞免疫通路、17条凋亡通路、11条细胞生长与增殖通路。结论:中药核心配伍从机体免疫、凋亡、细胞增殖、代谢等多个方面综合发挥对OA的治疗作用。

Objective： To explore the core compatibility of Chinese medicine and their possible mechanism in the treatment of osteoarthritis （OA）. Methods： The Chinese compound recipes for OA treatment were searched in Chinese Biomedical Literature Database. The drug database was established by Access2003 and the drug compatibility networks were estabhshed by complex networks. The top 5 drugs which showed higher network relative centrality were taken as the core compatibility. The human active target proteins of main effective ingredients in Chinese medicine and OA related genes were searched, and the molecular networks of Chinese medicine target proteins and OA related genes were performed the confluence analysis by ingenuity pathway analysis （ IPA ） platform. Results： Totally 208 compound recipes were included, and Radix Achyranthis Bidentatae ,Radix Angelicae Sinensis ,Radix Glycyrrhizae, Cortex Eucommiae and Radix Paeoniae Alba were taken as the core compatibility. There were 97 target proteins and 365 OA related genes. The function of OA related genes and Chinese medicine target proteins molecular networks that with higher correlation scores both involved the connective tissue, skeletal and muscular diseases, inflammation and metabolic diseases. The network confluence analysis showed that the common molecules of direct action in the molecular networks of OA related genes and Chinese medicine target proteins included TP53, PTPN1, RELA,DNMT1 ,NFKB1 and VDR. In the classical pathways of OA related genes,there were 3 kinds of pathways that showed higher correlation with Chinese medicine target proteins, including 28 pathways of cell immune, 17 pathways of cell apoptosis and 11 pathways of cell growth and proliferation. Conclusion： The core compatibility of Chinese medicine play the therapeutic role in the treatment of osteoarthritis through immune, apoptosis, cell proliferation and metabolism.