基于生物信息学分析整合组方规律发掘白脉软膏治疗白脉病的作用机制及其功效组配伍特点

Investigation on Compatibility Characteristics and Mechanism of Baimai Ointment in Intervening "White Vein" by Integrating Bioinformatics Analysis and Prescription Rule Discovery

目的:基于系统理论思想从网络视角探索白脉软膏治疗白脉病的作用机制及其功效组配伍特点,为指导临床合理用药提供生物学依据。方法:利用中医药百科全书数据库(ETCM)和中医药整合药理学研究平台(TCMIP)获得白脉软膏的化学成分及对应的候选靶标谱,根据白脉病的临床病理学特征,以神经病理性疼痛、炎性疼痛、慢性疼痛和腰椎间盘突出根性神经痛4种疾病/症状为关注点,在人类表型本体(HPO),DisGeNET等数据库收集白脉病相关的疾病基因集,构建"白脉软膏活性成分靶标-白脉病相关基因集"相互作用网络,在此基础上筛选其核心网络节点并进行富集分析,探讨白脉软膏组方中活血通络组(姜黄、麝香、碱花),行气止痛组(肉豆蔻、甘松、藏菖蒲),温经散寒通络组(干姜、花椒、藏茴香)和健脾温肾强骨组(阳起石、甘草)4个功效组配伍治疗白脉病的作用机制。结果:白脉软膏所含4个功效组富集的通路主要分布于神经系统功能、炎症-免疫系统调节和机体能量代谢3个模块,各模块间通过共有靶标基因关联又各有侧重。其中,活血通络组和行气止痛组对神经系统功能的调节作用可概括为活血补气和醒神开窍;行气止痛组和健脾温肾强骨组主要用于推动机体气机运行,促进血液化生,增强机体免疫,维持炎症-免疫系统的调节;健脾温肾强骨组和温经散寒通络组主要通过补脾益气及温热药性来调节机体能量代谢;全方分析侧重挖掘白脉软膏从多维度、多层次干预白脉病的作用机制,各功效组强调其在神经系统功能、炎症-免疫调节、机体能量代谢中各有侧重的作用特点,2种网络分析模式相互补充、相互印证。结论:白脉软膏主要通过调节神经系统功能、维持机体炎症-免疫系统平衡及干预机体能量代谢的整合效应来发挥其对白脉病的治疗作用,相关研究可为白脉软膏作用机制的深入阐释提供参考,并有助于指导其临床合理用药。

Objective:To explore the mechanism and compatibility characteristics of Baimai ointment(BMO)in the treatment of white vein disease from the network perspective based on system theory,so as to provide biological basis for its clinical application.Method:The chemical components and the corresponding candidate target spectra of BMO were obtained from The Encyclopedia of Traditional Chinese Medicine(ETCM)and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP).According to the clinicopathological characteristics of white vein disease,focusing on four diseases/symptoms including neuropathic pain,inflammatory pain,chronic pain and lumbar disc herniation root neuralgia,the gene sets related to white vein disease were collected in Human Phenotype Ontology(HPO),DisGeNET and other databases,then the interaction network of the targets of active components in BMO-gene sets related to white vein disease was constructed.On this basis,the hub network nodes were selected and enriched for exploring the mechanism of four functional groups of BMO in the treatment of white vein disease such as Huoxue Tongluo group(Curcumae Longae Rhizoma,Moschus,Tronae),Xingqi Zhitong group(Myristicae Semen,Nardostachyos Radix et Rhizoma,Acori Calami Rhizoma),Wenjing Sanhan Tongluo group(Zingiberis Rhizoma,Zanthoxyli Pericarpium,Caraway)and Jianpi Wenshen Qianggu group(Actinolite,Glycyrrhizae Radix et Rhizoma).Result:The enriched pathways of the four functional groups in BMO were mainly distributed in three modules of nervous system function,inflammation-immune system regulation and body energy metabolism,and each module was connected by common target genes especially had its own focus.Among them,the regulation of nervous system function in Huoxue Tongluo group and Xingqi Zhitong group could be summarized as Huoxue Buqi and Xingshen Kaiqiao.Xingqi Zhitong group and Jianpi Wenshen Qianggu group were mainly used to promote the operation of Qi,promote blood metaplasia,enhance immunity and maintain the regulation of inflammation-immune system.Jianpi Wenshen Qianggu group and Wenjing Sanhan Tongluo group mainly regulated body energy metabolism by invigorating the spleen and supplementing Qi as well as warm-heat medicine.The whole formula focused on the multi-dimensional and multi-level mechanism of BMO in the intervention of white vein disease.Each functional group emphasized its respective characteristics in nervous system function,inflammation-immune regulation,and body energy metabolism.Two types of networks analysis models complemented and verified each other.Conclusion:BMO plays a role in the treatment of white vein disease mainly by regulating the function of nervous system,maintaining the balance of inflammation-immune system and interfering with energy metabolism.The relevant research results can provide reference for the in-depth exploration of the mechanism of BMO,and help to guide the clinical rational use of this preparation.