目的 基于网络药理学与分子对接技术，阐释通脉降糖胶囊治疗糖尿病肾病的活性成分、潜在靶点及信号通路，为其临床应用提供理论依据。方法 利用TCMSP、ETCM、HERB数据库筛选通脉降糖胶囊的活性成分及靶点；通过GeneCards、OMIM数据库获取糖尿病肾病靶点，取交集得到潜在治疗靶点。采用STRING数据库与Cytoscape软件构建蛋白相互作用（PPI）网络并筛选核心靶点；通过DAVID数据库进行基因本体论（GO）与京都基因和基因组百科全书（KEGG）富集分析；构建“药物–成分–靶点–疾病”网络筛选核心成分；运用AutoDock Vina进行分子对接验证。结果 共获得通脉降糖胶囊活性成分135个，潜在治疗靶点304个。PPI网络拓扑分析确定蛋白激酶B1（Akt1）、肿瘤蛋白p53（TP53）、肿瘤坏死因子（TNF）、白细胞介素（IL）-6、胱天蛋白酶3（CASP3）、IL-1B、低氧诱导因子-1A（HIF-1A）、核因子-κB（NF-κB）1、信号转导与转录激活因子3（STAT3）、转化生长因子-β1（TGF-β1）为10个核心靶点。GO与KEGG富集分析显示，靶点显著富集于晚期糖基化终产物（AGEs）与其受体（RAGE）信号通路、IL-17信号通路、脂质与动脉粥样硬化通路及HIF-1信号通路等，涉及炎症反应、氧化应激、细胞凋亡与纤维化调控等过程。槲皮素、木犀草素、小檗碱、丹参酮II_A、黄芩苷、山柰酚、刺芒柄花素、毛蕊异黄酮、异鼠李素、阿魏酸为网络核心成分。分子对接表明，所有核心成分与核心靶点具有强烈结合活性。结论 通脉降糖胶囊可能通过上述核心成分作用于Akt1、TNF、IL-6、HIF-1A、TGF-β1等关键靶点，协同调控AGE-RAGE、PI3K/Akt、HIF-1、IL-17等信号通路，发挥抗炎、抗氧化、抗凋亡及抗纤维化等多重作用。

Objective To systematically elucidate the active components, potential targets, and signaling pathways of Tongmai Jiangtang Capsules in treatment of diabetic nephropathy by using network pharmacology and molecular docking, and to provide a theoretical basis for its clinical application. Methods Active components and targets of Tongmai Jiangtang Capsules were screened from TCMSP, ETCM, HERB, and other databases. Diabetic nephropathy-related targets were retrieved from GeneCards and OMIM, and the intersection was taken to obtain potential therapeutic targets. PPI network was constructed using the STRING database and Cytoscape, and core targets were identified through topological analysis. GO and KEGG enrichment analyses were performed via the DAVID database. A “drug-component-target-disease” network was constructed to identify core active components. Molecular docking was conducted with AutoDock Vina for validation. Results A total of 135 active components of Tongmai Jiangtang Capsules were obtained, along with 304 potential therapeutic targets. PPI network topology analysis identified ten core targets: Akt1, TP53, TNF, IL-6, CASP3, IL-1B, HIF-1A, NF-κB, STAT3, and TGF-β1. GO and KEGG enrichment analyses revealed that the targets were significantly enriched in the AGE-RAGE signaling pathway, IL-17 signaling pathway, lipid and atherosclerosis pathway, HIF-1 signaling pathway, and others, mainly involving inflammatory response, oxidative stress, apoptosis, and fibrosis regulation. Quercetin, luteolin, berberine, tanshinone II_A, baicalin, kaempferol, formononetin, calycosin, isorhamnetin, and ferulic acid were identified as the core components. Molecular docking showed that the binding energies of all core component has strong binding affinity. Conclusion Tongmai Jiangtang Capsules may exert anti-inflammatory, antioxidant, anti-apoptotic, and anti-fibrotic effects by acting on key targets such as Akt1, TNF, IL-6, HIF-1A, and TGF-β1 through core components like quercetin, luteolin, and berberine, synergistically modulating the AGE-RAGE, PI3K/Akt, HIF-1, IL-17, and other signaling pathways.

R286.7

陕西省教育厅科学研究计划项目（25JR059）