结合基因表达数据库(Gene Expression Omnibus，GEO)数据挖掘、网络药理学及分子对接技术，探讨大黄丹参药对干预糖尿病肾脏疾病的潜在作用机制。

通过中药系统药理学数据库，结合《中国药典》及文献获取大黄丹参的有效成分与潜在靶标。检索GEO数据库中糖尿病肾脏疾病相关肾小球数据集GSE30528、肾小管数据集GSE30529；在两类组织中分别进行差异分析，筛选探索性候选靶点。利用互作基因/蛋白质搜索工具(Search Tool for Retrieval of Interacting Genes/Proteins，STRING)数据库进行蛋白互作分析，借助Cytoscape软件构建靶点网络，使用R语言对关键靶标进行基因本体(Gene Ontology, GO)功能注释与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析，最后采用AutoDock Vina开展分子对接验证。

筛选出大黄丹参有效成分90个、潜在靶标150个，DKD候选差异靶标3 592个，共获得交集靶标43个。拓扑分析明确核心靶点为表皮生长因子受体、半胱天冬酶3、激酶插入结构域受体、丝裂原活化蛋白激酶1及细胞间黏附分子1，核心成分为大黄素、芦荟大黄素、丹参素、丹参酮ⅡA。GO功能富集于上皮细胞增殖与凋亡、细胞外信号调节激酶1/2级联反应及含胶原细胞外基质；KEGG主要富集于磷脂酰肌醇3-激酶/蛋白激酶B、丝裂原活化蛋白激酶、整合素及缺氧诱导因子-1信号通路。分子对接显示，大黄素和丹参酮ⅡA与核心靶点表皮生长因子受体的结合能分别为9.32、9.59 kcal/mol，均具有较好的理论结合活性。

大黄丹参药对可能通过多成分、多靶点、多通路网络参与糖尿病肾脏疾病相关病理过程；大黄素、丹参酮ⅡA及表皮生长因子受体相关信号网络可作为后续体内外验证的候选方向。

To explore the potential mechanism of the rhubarb-Salvia miltiorrhiza herb pair in the intervention of diabetic kidney disease (DKD) by integrating Gene Expression Omnibus (GEO) data mining, network pharmacology, and molecular docking techniques.

Active ingredients and potential targets of rhubarb-Salvia miltiorrhiza were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database combining with the Chinese Pharmacopoeia and relevant literature. The glomerular dataset GSE30528 and the tubular dataset GSE30529 related to DKD were retrieved from the GEO database, and differential analysis was performed in the two types of tissues to screen exploratory candidate targets. Protein-protein interaction analysis was performed using the STRING database, and the target network was constructed with Cytoscape software, while GO functional annotation and KEGG pathway enrichment analysis of key targets were conducted via R language. Finally, molecular docking verification was carried out using AutoDock Vina.

From rhubarb-Salvia miltiorrhiza, a total of 90 active ingredients, 150 potential targets, and 3, 592 candidate differential targets for DKD were screened out, yielding a total of 43 intersecting targets. Topological analysis identified the core targets as EGFR, CASP3, ICAM1, KDR, and MAPK1, and the core components as emodin, aloe-emodin, danshensu, and tanshinone ⅡA. Go enrichment involved epithelial cell proliferation and apoptosis, ERK1/2 cascade reaction, and collagen-containing extracellular matrix. KEGG enrichment was mainly observed in PI3K/Akt, MAPK, integrin, and HIF-1 signaling pathway. Molecular docking showed that the binding energies of emodin and tanshinone ⅡA to the core target EGFR were -9.32 and -9.59 kcal/mol, respectively, both exhibiting favorable theoretical binding activity.

The rhubarb-Salvia miltiorrhiza herb pair may participate in the pathological processes associated with DKD through a multi-component, multi-target, and multi-pathway network. The signal networks related to emodin, tanshinone ⅡA, and EGFR can serve as candidate directions for subsequent in-vivo and in-vitro verification.