摘要
目的类风湿关节炎(Rheumatoid Arthritis,RA)是一种发生在滑膜关节及其他器官系统的慢性进行性自身免疫性疾病,中医药治疗类风湿关节炎历史悠久,积累了丰富的临床应用经验,药对是中医临床遣药组方常用的配伍形式,如何从分子机制角度深入探索和发现药对中的不同成分之间的协同组合机制,目前还没有较为有效的定量研究方法。方法通过GEO差异基因分析筛选RA关键基因,并整合已知RA疾病相关靶点信息,利用STRING构建RA疾病PPI网络;选取两种经典药对:独活-桑寄生、黄柏-苍术,使用TCMID、ETCM数据库收集并整理两种药对的主要化学成分,预测并识别出药对中所有成分作用的潜在RA靶点;同时,提出基于通络扰动相似性的建模方法,挖掘药对中具有协同治疗作用的中药小分子组合,并对所作用靶点集进行GO功能注释与KEGG通路富集分析。结果通过GEO差异基因分析及TTD、DrugBank数据库收集与整理,共得到555个与RA相关的靶点基因;通过靶点预测与识别,获得独活-桑寄生药对53个成分及其作用的52个潜在RA靶点,黄柏-苍术药对得到32个成分及28个靶点;利用基于通路扰动相似性的计算方法,发现了独活-桑寄生中15对、黄柏-苍术中17对具有协同性的小分子组合。结论本文提出的基于通路扰动相似性的计算方法,能够阐明有效中药成分在治疗RA中存在的通路协同组合特征,从一个全新角度揭示了中药药对配伍的内在机制和规律,为后续深入研究打下扎实的基础。
Objective Rheumatoid Arthritis(RA)is a chronic and progressive autoimmune disease that occurs in synovial joints and other organ systems.Traditional Chinese medicine(TCM)has a long history of treating RA,and has accumulated rich clinical experience.Application experience shows that Chinese medicine pairs(CMPs)are commonly used in clinical prescriptions.However,at present,there is no clear and effective quantitative method on how to explore the combined effects of different components in CMPs from the perspective of molecular mechanisms.Methods We conducted differential gene analysis through GEO database,identified key RA genes,combined with known RA targets,and then input these genes into STRING to construct a PPI network of RA.Two classic CMPs were selected:DuHuoSangjisheng(DH-SJS)and HuangBai-Cangzhu(HB-CZ),the main components of the two CMPs were collected by using TCMID and ETCM databases.Next,we predicted and identified the set of potential targets where all components act.We proposed a modeling method based on the perturbation of the pathways,got the small molecules combination in the CMPs,and performed GO function and KEGG pathway enrichment analysis of the targets.Results Through GEO differential gene analysis and collection and sorting of TTD and DrugBank databases,we obtained 555 R A-related targets.Then,we carried out target prediction and identification of the ingredients,and obtained 53 ingredients and 52 targets of DH-SJS,and 32 ingredients and 28 targets of HB-CZ.Based on the proposed calculation method,we found a combination of small molecules with pathway synergy,and there were 15 pairs in DH-SJS and 17 pairs in HB-CZ.Conclusion The calculation method proposed in this paper could discover the synergistic combination characteristics of the effective components in different CMPs in the treatment of RA,revealed the internal mechanism and rules of CMPs compatibility from a new perspective,and laid a solid foundation for subsequent in-depth research.
作者
孙继佳
王睿瑞
张磊
刘保成
吕爱平
Sun Jijia;Wang Ruirui;Zhang Lei;Liu Baocheng;Lyu Aiping(Shanghai Traditional Chinese Medicine Health Service Collaborative Innovation Center,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China;Department of Mathematics and Physics,Shanghai University of Traditional Chinese Medicine,Shanghai 201203;Institute of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第6期2023-2035,共13页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
上海市卫计委员上海市中医药发展办公室上海市进一步加快中医药事业发展三年行动计划中医药传承创新平台建设子项目(ZY(2018-2020)-CCCX-2001-01):“互联网+中医健康服务”研究与转化平台,负责人:张磊
上海市卫健委中医药科研项目计划普通项目(2020JP002):基于计算建模方法的抗RA中药有效成分协同组合机制发现、优化及验证,负责人:孙继佳。
