基于网络药理学和分子对接探讨加味消脂利肝方治疗非酒精性脂肪性肝病的作用机制*

作者：余家乐1，2，李涵宇1，唐凌霄1，何文智1,2

单位：1.湖南中医药大学口腔医学院，湖南 长沙 410218； 2.湖南中医药大学中西医结合学院，湖南 长沙 410208

引用：引用：余家乐，李涵宇，唐凌霄，何文智.基于网络药理学和分子对接探讨加味消脂利肝方治疗非酒精性脂肪性肝病的作用机制[J].中医药导报,2026,32(5):33-40.

DOI：10.13862/j.cn43-1446/r.2026.05.006

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摘要：目的：探究加味消脂利肝方治疗非酒精性脂肪性肝病（NAFLD）的作用机制。方法：运用TCMSP/BATMAN/ETCM/HERB数据库，筛选加味消脂利肝方活性成分及靶点。通过GeneCards与CTD数据库获取NAFLD相关靶点，借助Cytoscape 3.9.1构建“药物-成分-靶点-疾病”调控网络，采用Cytoscape进行拓扑分析，筛选关键核心靶点。对共有靶点进行基因本体论（GO）富集分析、京都基因与基因组百科全书（KEGG）通路富集分析，通过AutoDock Tools对核心活性成分与关键靶点进行分子对接，验证其结合活性与构效关系。将SD大鼠随机分为空白组、模型组、中药组、西药组，每组9只。给药14 d后检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平；HE和油红O染色观察肝脏组织病理形态，并评定NAFLD活动度评分（NAS评分）；酶联免疫吸附试验（ELISA）检测大鼠血清肿瘤坏死因子-α（TNF-α）与白细胞介素-1β（IL-1β）水平；RT-qPCR检测肝组织丝氨酸/苏氨酸蛋白激酶1（Akt1）mRNA和表皮生长因子受体（EGFR）mRNA表达情况。结果：筛选出加味消脂利肝方药物中199个活性成分，交集靶点220个，包括5，6-二羟基-7-异丙基-1，1-二甲基-2，3-二氢菲-4-酮、槲皮素、山柰酚、泽泻醇B等主要活性成分，作用于Akt1、EGFR等关键靶点；KEGG通路富集分析得到183条通路；分子对接显示加味消脂利肝方中筛选出的活性成分与靶点均具有良好的结合活性。动物实验显示，模型组大鼠NAS评分高于空白组（P<0.01）；中药组、西药组大鼠NAS评分低于模型组（P<0.01）。模型组大鼠血清TNF-α、IL-1β、ALT、AST水平高于空白组（P<0.01）；中药组、西药组大鼠血清TNF-α、IL-1β、ALT、AST水平低于模型组（P<0.01）；中药组大鼠血清ALT水平低于西药组（P<0.05）。模型组大鼠血清TC、TG、LDL-C水平高于空白组，血清HDL-C水平低于空白组（P<0.01）。中药组、西药组大鼠血清TC、TG、LDL-C水平低于模型组，HDL-C水平高于模型组（P<0.01）；中药组大鼠血清TG水平低于西药组（P<0.01）。模型组大鼠肝组织Akt1 mRAN、EGFR mRAN相对表达量高于空白组（P<0.01）；中药组、西药组大鼠肝组织Akt1 mRNA、EGFR mRNA相对表达量低于模型组（P<0.01或P<0.05）。结论：加味消脂利肝方可降低NAFLD大鼠体内Akt1 mRNA、EGFR mRNA的表达，调节脂质代谢，控制炎症反应。

关键词：非酒精性脂肪性肝病；加味消脂利肝方；网络药理学；分子对接；大鼠

Abstract：

Objective: To explore the molecular mechanism of Jiawei Xiaozhi Ligan decoction (JXLD) on against non-alcoholic fatty liver disease (NAFLD). Methods: Bioactive constituents and their corresponding protein targets of JXLD were retrieved from the TCMSP, BATMAN, ETCM, and HERB databases. NAFLD-related genes were sourced from GeneCards and CTD. A "formulation-compound-target-pathology" regulatory network was built using Cytoscape 3.9.1, and topological parameters were analyzed by Cytoscape to identify core targets. Shared targets underwent Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Binding affinities between principal active ingredients and hub targets were evaluated via molecular docking using AutoDock Tools. For in vivo validation, SD rats were randomly divided into a blank group, a model group, a JXLD group, and a Western medicine group, with 9 rats in each group. Following 14 days of administration, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were assayed. Liver pathological changes were assessed by hematoxylin-eosin (H&E) and Oil Red O staining, alongside the NAFLD Activity Score (NAS). Serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were quantified via enzyme linked immunosorbent assay (ELISA). The hepatic expression levels of Akt1 mRNA and epidermal growth factor receptor (EGFR) mRNA were measured by RT-qPCR. Results: A total of 199 active compounds were identified from JXLD, intersecting with 220 NAFLD-related targets. Major components, including 5,6-dihydroxy-7-isopropyl-1,1-dimethyl-2,3-dihydrophenanthren-4-one, quercetin, kaempferol, and alisol B, mainly acted on key targets such as Akt1 and EGFR. KEGG analysis yielded 183 significant pathways. Molecular docking showed favorable binding interactions between the screened compounds and their respective targets. In animal experiments, the model group exhibited significantly elevated NAS scores compared with the blank group (P<0.01), whereas the JXLD group and Western medicine group showed lowere NAS scores than the model group (P<0.01). The serum levels of TNF-α, IL-1β, ALT, and AST in the model group were higher than those in the blank group (P<0.01). The serum levels of TNF-α, IL-1β, ALT, and AST in the JXLD group and the Western medicine group were lower than those in the model group (P<0.01). The serum level of ALT in the JXLD group was lower than that in the Western medicine group (P<0.01). The serum levels of TC, TG, and LDL-C in the model group were higher than those in the blank group, while the serum HDL-C level was lower than that in the blank group (P<0.01). The serum levels of TC, TG, and LDL-C in the JXLD group and the Western medicine group were lower than those in the model group, while the HDL-C level was higher than that in the model group (P<0.01). The serum TG level in the JXLD group was lower than that in the Western medicine group (P<0.01). The relative expression levels of Akt1 mRNA and EGFR mRNA in the liver tissue of the model group were higher than those in the blank group (P<0.01). The relative expression levels of Akt1 mRNA and EGFR mRNA in the liver tissue of the JXLD group and the Western medicine group were lower than those in the model group (P<0.01 or P<0.05). Conclusion: Jiawei Xiaozhi Ligan decoction can reduce the expression of Akt1 mRNA and EGFR mRNA in NAFLD rats, regulate lipid metabolism, and control the inflammatory response.

Key words：non-alcoholic fatty liver disease; Jiawei Xiaozhi Ligan decoction; network pharmacology; molecular docking; rat

发布时间：2026-05-23

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