基于文献数据挖掘和网络药理学分析的腰椎间盘突出症用药规律及作用机制研究

Study on the Medication Rule and Action Mechanism of Lumbar Disc Herniation Based on Literature Data Mining and Network Pharmacology Analysis

目的通过文献数据挖掘归纳分析出中药治疗腰椎间盘突出症的用药特点及规律,然后利用网络药理学的研究方法探讨高频组合中药治疗腰椎间盘突出症的潜在作用靶点及分子机制。方法系统检索中国知网(CNKI)、万方(WanFang Data)、维普(VIP)数据库中中药治疗腰椎间盘突出症的数据挖掘类文献,利用中医传承辅助平台中软件进行数据统计与分析,筛选出基于关联规则分析的中药治疗腰椎间盘突出症的高频组合,然后通过TCMSP等数据库收集这些高频组合中药的化学成分及所有有效活性成分并预测其作用靶点。通过公认的疾病数据库收集腰椎间盘突出症疾病靶点,然后将药物靶点与疾病靶点进行映射,并对关键靶点进行蛋白互作网络分析、GO功能富集分析和KEGG信号通路富集分析。结果研究共纳入24篇文献,处方总数共7233张,牛膝、当归、杜仲、甘草、熟地黄等是用药频次最多的药物,温性药、甘味药在四气五味中占比最多,中药药物归经频次最多的是肝经,基于关联规则分析得出的高频中药组合为杜仲、当归、熟地黄、牛膝、白芍、甘草。高频中药组合有效活性成分63个,药物作用靶点667个,疾病作用靶点447个,两者共有作用靶点65个,蛋白互作分析中药治疗腰椎间盘突出症的关键蛋白可能是AKT1、MAPK1、PIK3R1、PIK3CA、HRAS等,涉及的细胞生物过程1427个,细胞组成46个,分子功能81个。通路富集分析274条,其中包括VEGF信号通路、TNF信号通路、HIL-1信号通路、MAPK信号通路等。结论中药治疗腰椎间盘突出症以补益肝肾、活血化瘀药为主,同时兼以祛风寒湿药为辅。治疗腰椎间盘突出症的高频药物具有多靶点、多途径作用的特点,可能是通过影响血管生成、炎症因子、免疫调节等途径发挥治疗作用。

Objective To summarize and analyze the characteristics and rules of traditional Chinese medicine in the treatment of lumbar disc herniation through literature data mining,and then to explore the potential targets and molecular mechanism of high-frequency combination of traditional Chinese medicine in the treatment of lumbar disc herniation by the research method of network pharmacology.Methods The data mining literatures of traditional Chinese medicine for the treatment of lumbar disc herniation in the database of CNKI,WanFang and VIP were systematically searched,and the data were statistically analyzed by using the software of the traditional Chinese medicine inheritance support system(TCMISS).The high frequency combination of traditional Chinese medicine in the treatment of lumbar disc herniation based on association rule analysis was selected.Then the chemical constituents and all the active components of these high-frequency combinations of traditional Chinese medicine were collected through TCMSP and other databases and the action targets were predicted.The disease targets of lumbar disc herniation were collected through the recognized disease database,and then the drug targets were mapped to the disease targets,and the key targets were analyzed by protein interaction network analysis,GO functional enrichment analysis and KEGG signal pathway enrichment analysis.Results The study included 24 articles and a total of 7233 prescriptions.Achyranthes bidentata,Chinses angelica,Eucommia ulmoides,licorice,and prepared Rehmannia glutinosa were the most frequently used medicines.Warm and sweet herbs accounted for the largest proportion in the four natures and five flavors of drugs,and the most frequent channel tropism of traditional Chinese medicine was liver meridian.Based on association rules analysis,the high-frequency TCM combinations were Eucommia ulmoides,Angelica sinensis,prepared Rehmannia glutinosa,Achyranthes bidentata,Paeonia lactiflora and licorice.There are 63 active components,667 drug targets and 447 disease targets in the combinations of high-frequency traditional Chinese medicine and 65 common targets.Protein interaction analysis showed that the key proteins of traditional Chinese medicine in treating lumbar disc herniation may be AKT1,MAPK1,PIK3R1,PIK3CA and HRAS,involving 1427 cell biological processes,46 cell composition and 81 molecular functions.274 pathways,including VEGF signaling pathway,TNF signaling pathway,HIL-1 signaling pathway and MAPK signaling pathway,were enriched.Conclusion Traditional Chinese medicine in the treatment of lumbar disc herniation focuses on tonifying liver and kidney,promoting blood circulation and removing blood stasis,and combination of dispelling wind and cold dampness.High frequency drugs for the treatment of lumbar disc herniation have the characteristics of multi-target and multi-channel effects,which may play a therapeutic role by influencing angiogenesis,inflammatory factors,immune regulation and other ways.