从痰湿论治非酒精性脂肪性肝病的用药规律及作用机制分析

Medication Rules and Mechanism of Non-alcoholic Fatty Liver Disease from Sputum Dampness

目的:挖掘从痰湿论治非酒精性脂肪性肝病(NAFLD)的处方用药规律,分析核心处方药物发挥作用的潜在机制。方法:搜集从痰湿论治NAFLD的临床研究文献,对处方药物的性味、归经进行系统聚类与关联规则分析。得出从痰湿论治NAFLD的核心处方后,检索数据库获取药物有效成分作用靶点及疾病靶点,二者取交集后在STRING数据库构建蛋白质-蛋白质相互作用关系网络,并在Cytoscape中对所有交集靶点进行评分以获取核心靶点。对关键靶点进行基因本体功能富集分析、京都基因和基因组百科全书通路富集分析,并将分析结果导入Cytoscape软件构建中药活性成分-靶点-疾病通路网络图。结果:筛选后共得到119首方药,涉及153味药物,多为甘味、温性,以归肝、脾经多见。关联规则分析结果显示,山楂、茯苓、泽泻、白术、丹参、半夏和陈皮是治疗NAFLD的核心药物。聚类分析得到核心处方组合“山楂、决明子、泽泻、丹参、柴胡、郁金”,网络药理学分析结果显示,核心处方与NAFLD交集靶点有248个,信号转导及转录激活因子3和细胞外基质致癌基因是从痰湿论治NAFLD最核心的靶点。叉头框O、肿瘤坏死因子和磷脂酰肌醇3激酶-蛋白激酶B信号通路等是从痰湿论治NAFLD的主要信号通路。甲基庚烯酮、槲皮素及山柰酚等是核心处方发挥作用的主要有效成分。结论:从痰湿论治NAFLD以甘味、温性药物为主,离不开对肝、脾的调理,山楂、茯苓、泽泻、白术、丹参、半夏和陈皮是从痰湿论治NAFLD的常用药物;从痰湿论治NAFLD的核心处方主要通过参与调节脂质代谢、炎症反应和氧化应激等生物学过程,发挥对NAFLD的治疗作用。

OBJECTIVE:To explore the prescription rules of non-alcoholic fatty liver disease(NAFLD)from sputum dampness,and analyze the potential mechanism of core prescription drugs.METHODS:Clinical research literature on the treatment of NAFLD from phlegm dampness was collected,and systematic clustering and association rules analysis were carried out on taste and attribution of prescription drugs.After determining the core prescription for treating NAFLD from the perspective of phlegm-dampness theory,we searched the database to obtain the drug’s effective ingredient targets and disease targets.The intersection of these targets was used to construct a protein-protein interaction network in the STRING database.Subsequently,all intersecting targets were scored in Cytoscape to identify core targets.Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on key targets.The analysis results were imported into Cytoscape to construct a network diagram of active ingredients-targets-disease pathways for traditional Chinese medicine.RESULTS:After screening,a total of 119 prescriptions were obtained,including 153 kinds of drugs,which were sweet and warm,and were more common in the liver and spleen.Analysis of association rules showed that Crataegi Folium,Wolfiporia Cocos,Alisma Orientale,Atractylodes Macrocephala Koidz,Radix Salviae,Arum Ternatum Thunb and Citrus Reticulata were the core drugs for the treatment of NAFLD.Core prescription combination of“Crataegi Folium,Cassiae Semen,Alisma Orientale,Radix Salviae,Radix Bupleuri and Curcumae Radix”was obtained by cluster analysis.Network pharmacological analysis showed that there were 248 intersection targets between the core prescription and NAFLD,and the signal transduction and transcriptional activator 3 and myelocytomatosis oncogene cellular homolog were the core targets for the treatment of NAFLD from sputum wetness.Forkhead box O,tumor necrosis factor and phosphatidylinositol 3 kinase-protein kinase B signaling pathways were the main signaling pathways of phlegm-dampness treatment of NAFLD.Methyl heptenone,quercetin and kaempferol were the main effective components of the core prescription.CONCLUSIONS:The treatment of NAFLD from phlegm dampness is mainly sweet and warm medicine,which is inseparable from the regulation of liver and spleen,and Crataegi Folium,Wolfiporia Cocos,Alisma Orientale,Atractylodes Macrocephala Koidz,Radix Salviae,Arum Ternatum Thunb and Citrus Reticulata are commonly used drugs for the treatment of NAFLD from phlegm dampness,and the core prescription of NAFLD from phlegm dampness mainly plays a therapeutic role in NAFLD by participating into the regulation of lipid metabolism,inflammatory response,oxidative stress and other biological processes.