目的 基于网络药理学、分子对接及细胞实验探究当归补血汤抗糖尿病肾病（DN）的作用机制。方法 利用中药系统药理学数据库与分析平台（TCMSP）及中药综合数据库（TCMID），筛选当归补血汤中黄芪与当归的有效成分；通过UniProt和Swiss Target Prediction数据库，识别活性成分的相关靶点；利用GeneCards与OMIM数据库预测DN的潜在靶点；基于获取的数据，利用STRING数据库以及Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络及“药物-活性成分-靶点”网络。利用DAVID数据库对上述靶点进行了基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析。通过分子对接实验及细胞实验进行验证，揭示当归补血汤治疗DN的作用机制。结果 网络药理学分析，得到当归补血汤32个活性成分，与疾病交集靶点255个； KEGG通路富集结果显示，关键靶点主要参与晚期糖基化终末产物及其受体（AGE/RAGE）信号通路、脂质代谢异常导致的动脉粥样硬化通路等多个与免疫反应和炎症过程密切相关的信号通路。此外，分子对接研究表明，该方剂的主要化学成分对于AGE/RAGE信号通路上的主要靶点表现出良好的结合能力。细胞实验结果表明，当归补血汤能够抵抗HK-2细胞经高糖诱导产生的炎症反应，并且能够抑制AGE/RAGE信号通路上的核心蛋白表达。结论 当归补血汤可能通过抑制AGE/RAGE信号通路，减轻高糖所致的炎症反应，从而达到治疗DN的目的，可为当归补血汤深入研究提供方向。

Objective To investigate the mechanism of Danggui Buxue Decoction (DBD) against diabetic nephropathy (DN) based on network pharmacology, molecular docking and cell experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) were used to screen the active components of Astragalus membranaceus and Angelica sinensis in DBD. Potential targets of these active compounds were identified using the UniProt and Swiss Target Prediction databases. Disease-related targets of DN were retrieved from GeneCards and OMIM. Protein-protein interaction (PPI) networks and a "drug-active component-target" network were constructed using the STRING database and visualized with Cytoscape. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was performed using the DAVID database. The key findings were further validated through molecular docking and in vitro cell experiments. Results Network pharmacology analysis identified 32 active components in DBD and 255 overlapping targets associated with DN. KEGG pathway enrichment revealed that the core targets were primarily involved in the AGE/RAGE (advanced glycation end products/receptor for AGEs) signaling pathway, atherosclerosis pathways linked to lipid metabolism disorders, and other critical pathways related to immune response and inflammatory processes. Molecular docking studies demonstrated strong binding affinities between the major bioactive compounds of DBD and key targets in the AGE/RAGE pathway. In vitro experiments confirmed that DBD significantly attenuated high glucose-induced inflammatory responses in HK-2 cells and suppressed the expression of core proteins in the AGE/RAGE signaling pathway. Conclusion DBD may exert therapeutic effects against diabetic nephropathy by inhibiting the AGE/RAGE signaling pathway, thereby alleviating hyperglycemia-induced inflammation. These findings provide a scientific foundation for further research into the pharmacological mechanisms of DBD in DN treatment.

R285.5

江苏省基础研究计划自然科学基金-前沿引领技术基础研究专项（ BK20232014）