中成药治疗慢性乙型病毒性肝炎用药规律及核心药材网络药理学预测

Medication rule of Chinese patent medicine in treatment of chronic hepatitis B and network pharmacology mechanism analysis of core herbs

目的基于古今医案云平台分析中成药治疗慢性乙型病毒性肝炎的用药规律,并基于网络药学方法探究核心药材组合治疗慢性乙型病毒性肝炎的潜在作用机制,为慢性乙型病毒性肝炎的临床用药提供参考。方法收集药融云数据库中收录的治疗慢性乙型病毒性肝炎中成药,对其所含药味、功能主治等信息进行摘录,经过数据筛选、标准化处理,建立标准化医案数据库,利用古今医案云平台,从中药频次、中药属性、聚类分析、药物关联分析等方面进行数据挖掘,总结慢性乙型病毒性肝炎用药特点,筛选核心药材组合。采用网络药理学方法对核心药材进行靶点预测、蛋白质相互作用(PPI)分析、京都基因与基因组百科全书(KEGG)通路富集分析,构建“药材-成分-靶点-通路”网络,预测核心药材作用机制。结果药融云数据库共收载治疗慢性乙型病毒性肝炎中成药114种,除去不同剂型,共计80种,涉及中药材279味,其中用药频次较高的中药有黄芪、丹参、虎杖、当归等15味中药。药性多见于寒、平、微寒、温;药味多属甘、苦、辛味;归于肝、脾、肺、心4经的较多;药物功效以清热解毒占比最高。核心药材组合虎杖-白花蛇舌草-丹参的17个主要活性成分可作用于132个核心靶点,调控包括HIF-1、IL-17、PI3-Akt、TNF、乙型肝炎等信号通路。结论临床中成药治疗慢性乙型病毒性肝炎以疏肝健脾、清热利湿为主,同时兼以活血化瘀、补虚止痛,达到虚实同治的良好效果。核心药材虎杖-白花蛇舌草-丹参通过多个成分干预多个靶点、进而调控多条与慢性乙型病毒性肝炎相关的信号通路来发挥治疗作用。

Objective Based on the cloud platform of ancient and modern medical records,the medication rules of Chinese patent medicines(CPM)in the treatment of chronic hepatitis B(CHB)were analyzed,and the potential mechanism of core herbs in the treatment of CHB was explored based on the network pharmacy method,so as to provide reference for the clinical medication of CHB.Methods The CPM for the treatment of CHB included in the Yaorongyun database were collected,and the information such as the herbs and function of the CPM were extracted.After data screening and standardization,a standardized medical case database was established.Using the ancient and modern medical case cloud platform,data mining was carried out from the aspects of frequency statistics,correlation analysis,cluster analysis and complex network analysis,etc.,and the characteristics of CHB medication were summarized and the core herbs were screened.The target prediction,protein-protein interaction(PPI)analysis,KEGG pathway enrichment analysis and'herb-component-target-pathway'network construction of core herbs were carried out by network pharmacology method to explain the mechanism of core herbs.Results A total of 114 kinds of CPM for the treatment of chronic hepatitis CHB were collected.After removing different dosage forms,80 kinds of CPM were obtained,involving 279 kinds of herbs.Among them,15 kinds of herbs with a higher frequency of use for treating CHB were Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Polygoni Cuspidati Rhizoma et Radix,Angelicae Sinensis Radix,etc.The medicinal properties were more common in cold,mild,slightly cold and warm;the taste of the medicine was mostly sweet,bitter and pungent;it was mainly attributed to the four meridians of liver,spleen,lung and heart.The efficacy of drugs was the highest in heat-clearing and detoxifying.Drug association analysis identified ten groups of drug combinations.Four groups of clustering were obtained by cluster analysis.The 17 main active components of the core herbs could act on 132 core targets and regulate signaling pathways including HIF-1,IL-17,PI3-Akt,TNF,hepatitis B and other signaling pathways.Conclusion Clinical CPM in the treatment of CHB is mainly based on soothing liver and invigorating spleen,clearing heat and removing dampness,and at the same time,promoting blood circulation and removing blood stasis,tonifying deficiency and relieving pain,so as to achieve the good effect of simultaneous treatment of deficiency and excess.The core herbs Polygoni Cuspidati Rhizoma et Radix-Hedyotis diffusa-Salviae Miltiorrhizae Radix et Rhizoma intervenes in multiple targets through multiple components and regulates multiple signaling pathways related to CHB to play a therapeutic role.