目的 基于网络药理学和分子对接技术探讨分心木治疗肾炎的作用机制。方法 利用中药系统药理数据库和分析平台（TCMSP）数据库筛选分心木的活性成分，利用GeneCards、TTD和PharmGKB数据库筛选药物靶点和肾炎靶点，并取交集靶点，运用Cytoscape软件构建“药物–活性成分–靶点–疾病”网络，通过DAVID数据库进行交集靶点的基因本体（GO）和京都基因和基因组百科全书（KEGG）通路富集分析，通过STRING数据库筛选共同靶点并构建蛋白质相互作用（PPI）网络确定核心靶点。使用Autodock vina软件进行活性成分与靶点的分子对接，并通过Pymol软件和Discovery Studio 2019软件进行可视化分析。结果 共筛选出分心木中与肾炎相关的8个活性成分即柚皮素、鞣花酸、谷甾醇、山柰酚、槲皮素、二氢槲皮苷、二氢槲皮素和(+)-儿茶素，获得药物靶点233个和肾炎靶点3 258个，取交集后得到108个交集靶点。山柰酚、鞣花酸和谷甾醇等连接的边线较其他成分多，对应的靶点约占网络图中总靶点数的65%。GO富集分析显示分心木治疗肾炎主要涉及免疫炎症反应、凋亡过程负调控和血管通透性调控等过程。KEGG通路主要富集在磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）通路、晚期糖基化终产物及其受体（AGE-RAGE）和血管内皮生长因子（VEGF）通路。PPI网络确定核心靶点分别为蛋白激酶B1（Akt1）、表皮生长因子受体（EGFR）、酪氨酸蛋白激酶转化蛋白（SRC）、过氧化物酶体增殖物激活受体γ（PPARG）、基质金属蛋白酶9（MMP9）、前列腺素G/H合酶2（PTGS2）、雌激素受体1（ESR1）、B细胞淋巴瘤2（Bcl2）、表皮生长因子受体2（ERBB2）和细胞间黏附分子1（ICAM1）。谷甾醇、鞣花酸、柚皮素、槲皮素、山柰酚和Akt1、EGFR、MMP9、Bcl2、ESR1的结合能均小于-4.2 kcal/mol。结论 分心木可能通过多成分、多靶点、多通路协同作用治疗肾炎。

Objective To explore the mechanism of Diaphragma Juglandis Fructus in treatment of nephritis based on network pharmacology and molecular docking technology. Methods Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database was used to screen the active ingredients of Diaphragma Juglandis Fructus. GeneCards, TTD and PharmGKB databases were used to screen drug targets and nephritis targets, and intersection targets were taken. Cytoscape software was used to construct a “drug-active ingredient-target-disease” network. Gene ontology (GO) and Kyoto encyclopedia database of genes and genomes (KEGG) pathway enrichment analysis of intersection targets were performed through DAVID database. The common targets were screened by STRING database and the protein-protein interaction (PPI) network was constructed to determine the core targets. Autodock vina software was used for molecular docking of active components and targets, and visual analysis was performed by Pymol software and Discovery Studio 2019 software. Results A total of 8 active components related to nephritis in Diaphragma Juglandis Fructus were screened out, such as naringenin, ellagic acid, sitosterol, kaempferol, quercetin, astilbin, taxifolin and (+)-catechin. A total of 233 drug targets and 3 258 nephritis targets were obtained, and 108 intersection targets were obtained after intersection. The edge lines of kaempferol, ellagic acid and sitosterol were more than other components, and the corresponding targets accounted for about 65% of the total targets in the network diagram. GO enrichment analysis showed that Diaphragma Juglandis Fructus in treatment of nephritis mainly involved immune inflammatory response, negative regulation of apoptosis process and regulation of vascular permeability. The KEGG pathway was mainly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, advanced genetically engineered end products and their receptors (AGE-RAGE) and vascular endothelial growth factor (VEGF) pathway. The PPI network identified the core targets as protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), tyrosine protein kinase conversion protein (SRC), peroxisome proliferator-activated receptor γ (PPARG), matrix metalloproteinase 9 (MMP9), prostaglandin G/H synthase 2 (PTGS2), estrogen receptor 1 (ESR1), B-cell lymphoma 2 (Bcl2), epidermal growth factor receptor 2 (ERBB2) and intercellular adhesion molecule 1 (ICAM1). The binding energies of sitosterol, ellagic acid, naringenin, quercetin, kaempferol and Akt1, EGFR, MMP9, Bcl2, ESR1 were all less than -4.2 kcal/mol. Conclusion Diaphragma Juglandis Fructus may treat nephritis through synergistic action involving multiple components, targets, and pathways.

R287.3

江西省重点研发计划项目（2023BBF61014）