目的 基于网络药理学和分子对接技术探讨补阳还五汤对 2 型糖尿病（T2DM）和阿尔兹海默症（AD）“异 病同治”的作用机制。方法 借助 TCMSP、SymMap 等数据库检索和筛选补阳还五汤中 7 味组方中药的活性成 分，并利用 PharmMapper 服务器对活性成分进行靶点预测。通过 OMIM、DrugBank、GeneCards 及 Disgenet 数 据库收集 T2DM 和 AD 疾病相关靶点。对疾病相关靶点与活性成分作用靶点取交集，获得补阳还五汤“异病同 治”T2DM 和 AD 的潜在作用靶点。使用 STRING 数据库和 Cytoscape 软件分别构建潜在作用靶点的蛋白-蛋白 互作（PPI）网络和“药物-成分-靶点”网络，通过网络拓扑分析筛选出核心活性成分和核心靶点。并借助 Metascape 数据库对潜在作用靶点进行 GO 功能及 KEGG 通路富集分析。采用 AutoDock 软件对筛选出的核心活 性成分和核心靶点进行分子对接验证。结果 94 个补阳还五汤活性成分可作用于 342 个蛋白靶点，与 3 140 个 AD 疾病相关靶点和 1 708 个 T2DM 疾病相关靶点比对后，得到 100 个潜在作用靶点（交集靶点）。GO 功能富集 分析显示，潜在作用靶点主要参与 MAPK 级联调控、激素介导的信号通路、细胞对脂质的反应、调节炎症反 应等生物过程。KEGG 通路富集分析得到 MAPK、PI3K/Akt、FoxO、AGE/RAGE、胰岛素抵抗、脂质和动脉粥 样硬化、非酒精性脂肪肝等通路。PPI 和“药物-成分-靶点”网络拓扑分析筛选出 MAPK8、MAPK14、 GSK3B、PPARG 等 10 个核心靶点，以及芍药苷、苯甲酰芍药苷、（+）-儿茶素等 10 个核心活性成分，分子对 接结果表明上述成分与靶点均有较强的结合能力。结论 补阳还五汤可能通过芍药苷、儿茶素等核心成分，作 用于 PPARG、GSK3B 等关键靶点，参与调控 MAPK、PI3K/Akt 等信号通路，进而发挥“异病同治”T2DM 和 AD 的作用。

Objective To explore the mechanism of Buyang Huanwu Decoction for “treating different diseases with same therapies” in type 2 diabetes mellitus （T2DM） and Alzheimer’s disease （AD） based on network pharmacology and molecular docking techniques. Methods Firstly，the active ingredients of seven herbs in Buyang Huanwu Decoction were searched and screened by TCMSP，SymMap and other databases，the target prediction of these active ingredients was carried out by PharmMapper. The disease targets of T2DM and AD were collected from OMIM， DrugBank， GeneCards and Disgenet databases. The potential targets of Buyang Huanwu Decoction for “treating different diseases with same therapies” in T2DM and AD were obtained by intersecting with targets of active ingredients and the disease targets. Then STRING database and Cytoscape software were used to construct the PPI network and “herbs-components-targets” network， respectively. The core targets and pharmacodynamic components were screened through network topology analysis. Furthermore， GO functional and KEGG enrichment analysis was performed for potential targets using Metascape database. Finally，AutoDock software was used to verify the molecular docking between the selected components and targets. Results Ninety-four active components of Buyang Huanwu Decoction can act on 342 protein targets，and 100 intersection targets were obtained by comparing with 3 140 AD targets and 1708 T2DM targets. GO functional enrichment analysis showed that these targets were mainly involved in MAPK cascade-mediated regulation，hormone-mediated signaling pathways，cellular response to lipids，regulation of inflammation response and other biological processes. MAPK，PI3K/Akt，FoxO，AGE/RAGE， insulin resistance， lipid and atherosclerosis， and non-alcoholic fatty liver signaling pathway were significantly enriched in KEGG analysis. PPI and topology analysis of “herbs-components-targets” network were used to screen out 10 core targets such as MAPK8，MAPK14，GSK3B，PPARG，and 10 core pharmacodynamic components such as paeoniflorin，benzoyl paeoniflorin，（+）-catechin. The results of molecular docking showed that these components had strong binding ability to the targets. Conclusion The core components of Buyang Huanwu Decoction，such as paeoniflorin and catechin，may act on PPARG，GSK3B and other key targets，and participate in the regulation of signaling pathways including MAPK and PI3K/Akt，which play a role in “treating different diseases with the same therapies” of T2DM and AD.

R285.5；R857.3

黑龙江省中医药管理局科研项目（ZHY2023-051）；中央支持地方高校改革发展资金人才培养项目［黑财教（2021）137号文件］；黑龙江 中医药大学科研基金项目（201819，2019BJP01，2018pt04）