基于数据挖掘及网络药理学探讨何赛萍教授治疗月经后期用药规律及机制

Explore the Medication Rules and Mechanisms of Professor HE Saiping Involved in the Treatment of Delayed Menstruation Based on Data Mining and Network Pharmacology

[目的]探究何赛萍教授治疗月经后期的临床用药规律,预测核心药物的潜在作用机制。[方法]搜集2019年1月1日至2021年6月30日何教授门诊诊治的月经后期女性的初诊处方,建立处方数据库。应用Excel 2013和SPSS 26.0软件对处方进行频次统计、聚类和关联规则分析,并利用网络药理学技术预测核心药物组合的作用机制。[结果]共纳入120首有效处方,包括154味中药。频次前5的药味为当归、白术、梅花、茯苓和菟丝子,多味甘、辛,性平,归脾、肝、肺经。结果显示,“当归-白术-梅花-茯苓”是治疗月经后期的核心药物组合;经筛选后获得“当归-白术-梅花-茯苓”的关键活性成分5个,包括β-谷甾醇、(-)-β-花柏烯、豆甾醇、常春藤皂苷元和苍术酮;经拓扑分析得到其治疗月经后期的7个关键靶点,包括肿瘤坏死因子(tumor necrosis factor,TNF)、β2-肾上腺素受体(β2-drenergic receptor,ADRB2)、去甲肾上腺素转运体(norepinephrine transporter,SLC6A2)、90 kDa热休克蛋白AA1(heat shock protein 90 kDa alpha1,HSP90AA1)、毒蕈碱型胆碱能受体1(cholinergic receptor muscarinic 1,CHRM1)、多巴胺D2受体(dopamine D2 receptor,DRD2)和钾电压阀门通道亚家族H成员2(potassium voltage-gated channel subfamily H member 2,KCNH2)。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析结果主要涉及磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinase B,PI3K-Akt)信号通路、环磷酸腺苷(cyclic adenosine monophosphate,cAMP)信号通路、环磷酸鸟苷-蛋白激酶G(cyclic guanosine monophosphate-protein kinases G,cGMP-PKG)信号通路等多种信号通路。[结论]何教授临床诊治月经后期时,在补肾的基础上更重视疏肝健脾、养血调经,以促进女性气血调和,月经按时来潮。其核心药物组合“当归-白术-梅花-茯苓”治疗月经后期的潜在靶点主要参与调节激素水平、生成血管壁、促进卵泡生长发育、降低炎症反应等生物学过程。本研究为中医药治疗月经后期提供了参考依据,并为进一步挖掘其作用机制提供了方向。

[Objective] To explore the clinical medication rules and to provide potential mechanisms of core herbs in the treatment of delayed menstruation(DM). [Methods] The prescriptions of women with DM were collected from the expert clinic of Professor HE Saiping from January 1,2019 to June 30,2021,and the prescription database was established. The Excel 2013 and SPSS 26.0 software were used to analyze the frequency statistics,clustering and association rule analysis. Network pharmacology was used to predict the potential mechanisms of core herb combinations. [Results] A total of 120 prescriptions were collected,involving 154 kinds of Chinese herbs. The top 5 Chinese herbs in frequency were Angelicae Sinensis(Danggui),Atractylodes Macrocephala Rhizoma(Baizhu),Mume Flos(Meihua),Poria cocos(Fuling) and Semen Cuscutae(Tusizi). Five tastes of Chinese herbs were mainly sweet and pungent,four properties were mainly flat,and meridian tropism was mainly the spleen,liver and lung. The herb pairs Angelicae Sinensis(Danggui)-Atractylodes Macrocephala Rhizoma(Baizhu)-Mume Flos(Meihua)-Poria cocos(Fuling) had the highest confidence in association rules analysis and were grouped in systematic cluster analysis. Five key active components of the herb pairs Angelicae Sinensis(Danggui)-Atractylodes Macrocephala Rhizoma(Baizhu)-Mume Flos(Meihua)-Poria cocos(Fuling) were obtained after screening,including β-sitosterol,β-chamigrene,stigmasterol,hederagenin and atractylone. Topological analysis showed 7 key targets for the treatment of DM,including tumor necrosis factor(TNF),β2-drenergic receptor(ADRB2),norepinephrine transporter(SLC6A2),heat shock protein 90 kDa alpha1(HSP90AA1),cholinergic receptor muscarinic 1(CHRM1),dopamine D2 receptor(DRD2),potassium voltage-gated channel subfamily H member 2(KCNH2). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis suggested that phosphatidylinositol-3-kinase-protein kinase B(PI3KAkt) signaling pathway,cyclic adenosine monophosphate(cAMP) signaling pathway,cyclic guanosine monophosphate-protein kinases G(cGMP-PKG) signaling pathway and other signaling pathways were mainly involved. [Conclusion] In the clinical diagnosis and treatment of DM,on the basis of tonifying the kidney,Professor HE pays more attention to soothing the liver and invigorating the spleen,nourishing blood and regulating menstruation,so as to promote the harmonization of female Qi and blood and timely menstruation. The potential targets and mechanisms of the core herbs combination Angelicae Sinensis(Danggui)-Atractylodes Macrocephala Rhizoma(Baizhu)-Mume Flos(Meihua)-Poria cocos(Fuling) in the treatment of DM were mainly involved in the biological processes of regulating hormone levels,generating blood vessel wall,promoting follicular growth and development,reducing inflammatory response. This study provides a reference for the treatment of DM with Chinese herbs and a direction to further explore its potential mechanism.