中医药治疗青春期功能失调性子宫出血的用药规律及新筛选方作用机制的网络药理学研究

Network Pharmocology Study on the Medication Rules of Puberty Dysfunctional Uterine Bleeding and the Mechnisms of New Screening Prescription

目的:探讨中医药治疗青春期功能失调性子宫出血(DUB)的组方用药规律及作用机制。方法:收集运用中药方剂治疗青春期DUB的文献,对文献所含方剂中涉及的中药进行频数、性味、归经及关联规则分析,并挖掘出潜在新方。通过检索TCMSP、GeneCards、OMIM数据库,收集新方中药物有效成分的靶点与疾病靶点并取交集,利用CytoscapeV3.9.0构建“青春期DUB-药物-化合物-靶点”网络,采用STRING平台、David数据库对关键靶点进行PPI网络分析及KEGG通路分析,并运用PubChem、Uniport、PDB数据库,AutoDockVina、PyMol软件对药物有效活性成分与关键靶标作分子对接。结果:共筛选出154个中药复方,包含药物143味,其中药性以温、平为主,药味以甘、苦为主,归经以肝经、肾经、脾经为主;常用药对有黄芪-白术、女贞子-墨旱莲、熟地黄-山茱萸等;挖掘出潜在4个新方组合。新方2(党参+升麻+黄芪+女贞子+墨旱莲)治疗青春期DUB的关键成分有槲皮素和木犀草素等,关键靶点为Akt激酶1(AKT1)、血管内皮生长因子(VEGFA)等,主要通路为癌症通路(Pathways in cancer)、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路等。结论:中医主要从肝肾论治青春期DUB,网络药理学与分子对接结果表明新方药物治疗青春期DUB的机制可能与其止血、抗炎及子宫内膜修复有关。

Objective:To explore the rules of formula use and mechanism of action of traditional Chinese medicine in the treatment of adolescent dysfunctional uterine bleeding.Methods:We collected literature on the use of Chinese herbal prescriptions for the treatment of adolescent dysfunctional uterine bleeding,analyzed the frequency,qi and flavor,and meridian entry of the Chinese herbal medicines involved in the prescriptions contained in the literature,as well as association rules and mined potential new prescriptions.Furthermore,the targets of each active ingredient in the new formula and disease targets were collected was taken by searching TCMSP,GeneCards and OMIM databases and get the intersection.Then Adolescent dysfunctional uterine bleeding-drug-ingredient-target network was constructed using CytoscapeV3.9.0.The STRING platform and David database were used to perform protein interaction network analysis as well as Kyoto gene and Genome Encyclopedia(KEGG)pathway analysis.And using PubChem,Uniport and PDB databases,AutoDockVina and PyMol software were used to make molecular docking with the drug active ingredients and key targets.Results:A total of 154 prescriptions were screened out including 143 Chinese herbs,of which the"qi"mainly included warm and calm;the"flavor"mainly included sweetness and bitterness;the main meridian entry was liver meridian(LR),followed by kidney meridian(KI)and spleen meridian(SP)in order.The commonly used couplet medicines consisted of Huangqi(Astragali Radix)-Baizhu(Atractylodis Macrocephalae Rhizoma),Nvzhenzi(Ligustri Lucidi Fructus)-Mohanlian(Ecliptae Herba),Shudihuang(Rehmanniae Radix Praeparata)-Shanzhuyu(Corni Fructus),etc;four potential new prescriptions were excavated.Combined with the analysis of data mining results,the key components of new prescription 2[Dangshen(Codonopsis Pilosula)+Shengma(Cimicifugae Rhizoma)+Huangqi(Astragali Radix)+Nvzhenzi(Ligustri Lucidi Fructus)+Mohanlian(Ecliptae Herba)]in the treatment of adolescent dysfunctional uterine bleeding were quercetin,luteolin,etc;the core target was AKT1,VEGFA,etc;the main pathways were Pathways in cancer,PI3K-AKT signaling pathway,etc.Conclusion:According to the results of data mining,it is clear that TCM mainly treats dysfunctional uterine bleeding in adolescence from LR and KI,and the results of network pharmacology and molecular docking suggest that prescription 2 for dysfunctional uterine bleeding in adolescence may be related to its stanch bleeding anti-inflammatory and endometrial repair.