摘要
目的整合多数据库资源,结合动脉粥样硬化(AS)疾病时空效应的特点,针对性筛选有效中药,以更好地指导临床合理用药。方法通过TCMIP、GeneCards、OMIM数据库获取AS及时空效应表型的相关靶点;基于上述靶点,通过TCMIP数据库“整合药理学分析工具集合”的“反向查找中药”功能,筛选血管内皮功能障碍(VED)、血管内皮损伤(VEI)、粥样斑块形成(PF)3个时间阶段及骨髓微环境(BMM)空间过程的防治中药;通过String、WebGestalt数据库对AS时空效应防治中药进行蛋白互作及GO、KEGG富集分析;通过R语言构建弦图与热图,对有效中药-时空效应进行关联性、差异性及最佳用药配伍聚焦。结果收集AS-VED、AS-VEI、AS-PF、AS-BMM共同靶点分别为924、935、885、1024个;反向查找中药结果显示,高良姜、漏芦、葛根、降香等可预防早期VED,牡荆叶、茜草、高良姜、漏芦等可治疗中期VEI,吴茱萸、急性子、葛根、降香等可消退晚期PF,皂角刺、香加皮、益母草、三棱、瓜蒌等在BMM中发挥作用,其作用机制可能与激活Rap1、Hippo、MAPK、Toll-like、TNF、AMPK、PI3K-AKT、NF-κB等多信号通路,调控AKT1、IL-6、INS、TNF、NR3C1、PPARG、PTGS2等多靶点,以“多药物-多靶点-多通路”模式在防治AS进程中发挥作用有关。结论本研究筛选出针对特异时间阶段与空间过程的中药,实现了微观层次上的辨证论治,为中医药防治AS提供了针对性的中药及靶点和通路的可能,为中医药辅助干细胞疗法提供思路。
Objective To integrate multi-database resources to select effective Chinese materia medica combined with the characteristics of spatiotemporal effect of atherosclerosis(AS);To better guide the rational medication in clinic.Methods The related targets of atherosclerosis and“spatiotemporal effect”phenotype were obtained by TCMIP,GeneCards and OMIM database,and TCM prevention and treatment of“time effect”of vascular endothelial dysfunction(VED),vascular endothelial injury(VEI),plaque formation(PF)and“space effect”of bone marrow microenvironment(BMM)were screened through the function of“reverse search for Chinese materia medica”in the collection of integrated pharmacological analysis tools in TCMIP database.The enrichment analysis of PPI,GO and KEGG was carried out on TCM prevention and treatment for spatiotemporal effect of AS through String and WebGestalt database;chord map and heat map were constructed by R language to focus on the correlation and difference of“effective Chinese materia medica spatiotemporal”and the best compatibility of medicine.Results The common targets of AS-VED,AS-VEI,AS-PF and AS-BMM were 924,935,885 and 1024 respectively.The results of reverse search of Chinese materia medica showed that Alpiniae Officinarum Rhizoma,Rhapontici Radix,Puerariae Lobatue Radix,and Dalbergiae Odoriferae Lignum could prevent vascular endothelial dysfunction in the early stage;Viticis Negundo Folium,Rubiae Radix et Rhizoma,Alpiniae Officinarum Rhizoma,Rhapontici Radix could treat vascular endothelial injury in the middle stage;Euodiae Fructus,Impatientis Semen,Puerariae Lobatue Radix,and Dalbergiae Odoriferae Lignum could eliminate atherosclerotic plaque in the advanced stage,and Chinese materia medica such as Gleditsiae Spina,Periplocae Cortex,Leonuri Herba,Sparganii Rhizoma,and Trichosanthis Fructus could play a role in bone marrow microenvironment,and their mechanism may be related to activating Rap1,Hippo,MAPK,Toll-like,TNF,AMPK,PI3K-AKT,NF-κB signal pathway and regulating multiple targets
作者
傅馨莹
孙正骥
吴露
张伟
FU Xinying;SUN Zhengji;WU Lu;ZHANG Wei(Hunan University of Chinese Medicine,Changsha 410208,China;Liuyang Hospital Affiliated to Hunan University of Chinese Medicine,Liuyang 410300,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2021年第4期32-40,共9页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(81774032)
湖南省自然科学基金杰出青年基金(2020JJ2024)
湖南省自然科学基金青年基金(2018JJ3391)
湖南省教育厅科学研究重点项目(19A374)
湖南中医药大学研究生培养质量工程专项(2020CX62)。
关键词
整合药理学
动脉粥样硬化
时空效应
血管内皮细胞
中医药
integrated pharmacology
atherosclerosis
spatiotemporal effect
vascular endothelial cells
TCM
