中医药治疗酒精性肝病的组方用药规律及作用机制研究

Analysis of Prescription Medication Rules and Mechanism of Action of Traditional Chinese Medicine in the Treatment of Alcoholic Liver Disease

目的基于数据挖掘和网络药理学技术研究中医药治疗酒精性肝病(ALD)的组方用药规律及潜在作用机制。方法检索中国知网、万方数据库、中国生物医学文献数据库和维普中文期刊收录的中医药治疗ALD的相关方剂,根据筛选条件整理后,使用IBM SPSS Statistics 27.0、IBM SPSS Modeler 18软件对纳入方剂的中药进行组方规律、关联规则分析,归纳中药治疗ALD的用药规律,获得核心药物组合。以网络药理学技术,筛选中医药干预ALD核心药物组合的活性成分及其作用靶点;用基因本体(GO)和京都基因与基因组百科全书(KEGG)对主要作用靶点进行富集分析,并以分子对接技术加以验证。结果共纳入治疗ALD的方剂143首,涉及中药222味,使用频次≥25次的高频中药28味,关联规则分析得到8个核心药物组合。其中“茯苓-白术-茵陈”与ALD交集靶点215个,包括蛋白激酶B(AKT1)、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)、白细胞介素1β(IL-1β)、非受体酪氨酸激酶(SRC)、表皮生长因子受体(EGFR)等6个核心靶点,涉及信号通路168条,主要包括癌症通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路、化学致癌-活性氧及脂质-动脉粥样硬化等。分子对接结果显示啤酒甾醇、芫花素、去甲氧基茵陈色原酮等主要活性成分与AKT1结合能力较好。结论核心药组“茯苓-白术-茵陈”的主要活性成分可通过作用于AKT1、TNF、VEGFA等关键靶点蛋白,参与PI3K/AKT等关键信号通路的调控,进而发挥抑制炎症反应及细胞凋亡、减缓肝纤维化、促进肝细胞修复的作用,可为中医药治疗ALD研究提供数据支撑与理论指导。

Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine(TCM)in the treatment of alcoholic liver disease(ALD)based on the technology of data mining and network pharmacology. Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases. After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules. Then,the medication rules of TCM in the treatment of ALD were summarized, and the core drug combinations were obtained. Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology. GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets. Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 high frequency Chinese medicine were used with a frequency ≥ 25 times. Eight core drug combinations were obtained by associations rule analysis. It has been found that there are 215 intersection targets between “Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae” and ALD, including six core targets of AKT1, TNF, VEGFA,IL-1β,SRC,EGFR. One hundred and sixty-eight of signaling pathways are involved,including cancer pathways, PI3K/AKT signaling pathways, chemical carcinogenesis-reactive oxygen species, lipid and atherosclerosis, etc. Molecular docking results showed that the main active components including cerevisterol, genkwanin and demethoxycapillarisin had good binding ability to AKT1. Conclusion The main active ingredients in “Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae” can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins(AKT1,TNF,and VEGFA) . Subsequently, they play a role in inhibiting inflammatory response and apoptosis, slowing down liver fibrosis, and promoting hepatocyte repair. This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.