【摘要】 目的 借助网络药理学研究方法，初步探索知葛通脉颗粒治疗2型糖尿病下肢动脉粥样硬化性病变的靶点和机制，为进一步研究提供相关理论支持和线索。方法 通过TCMSP数据库检索、文献补充，筛选知葛通脉颗粒有效成分及效用靶点，通过GeneCards、OMIM等数据库挖掘2型糖尿病LEAD靶点，取药物与疾病的交集靶点；利用STRING11.5制作PPI网络图，并通过PPI网络拓扑关系分析知葛通脉颗粒治疗2型糖尿病LEAD的关键靶点；构建“药物-成分-靶点”关系图，筛选中药颗粒核心成分。在Metascape平台进行GO、KEGG富集分析，探索药物治疗疾病的潜在机制，构建“成分-靶点-通路”图。最后，通过AutoDockTools 1.5.6进行分子对接，验证药物活性成分与疾病靶点之间的反应活性。结果 研究获得知葛通脉颗粒有效成分71种，潜在靶点261个，与DLEAD交集靶点107个，筛选出核心成分槲皮素、木犀草素、山柰酚、芒柄花黄素、异鼠李素、去水淫羊藿黄素、薯蓣皂苷元、β-谷甾醇、金圣草素、豆甾醇，关键靶点AKT1、IL-6、TNF、TP53、VEGFA、IL-1B。相关作用通路有183条，作用通路主要涉及MAPK、糖尿病并发症中的AGE-RAGE、HIF-1信号通路等。对接结果显示中药成分与疾病靶点之间可较好地结合。结论 知葛通脉颗粒可通过槲皮素、木犀草素、山柰酚、芒柄花黄素、异鼠李素、去水淫羊藿黄素、薯蓣皂苷元、β-谷甾醇、金圣草素、豆甾醇等关键有效成分作用于AKT1、IL-6、TNF、TP53、VEGFA、IL-1B等关键靶点，调节MAPK、糖尿病并发症中的AGE-RAGE、HIF-1等信号通路，多靶点、多通路协同发挥对DLEAD的治疗作用。更多还原

【Abstract】 Objective To explore the targets and mechanisms of Zhige Tongmai Granules for treating lower extremity atherosclerotic disease(LEAD) in type 2 diabetes mellitus(T2DM) patients based on network pharmacology technology, and to provide relevant theories and clues for further study. Methods Effective ingredients and targets of Zhige Tongmai Granules were screened by searching TCMSP database, supplemented by related papers. Relevant targets of LEAD of T2DM were detected through GeneCards, OMIM, and other databases, and the intersectional targets of drugs and diseases were selected. The PPI net was made on STRING11.5, and the crucial targets of Zhige Tongmai Granules for treating diabetic LEAD(DLEAD) were obtained by topological analysis of PPI. Drugs-Active Components-Targets network was constructed to screen the core components of traditional Chinese medicine granules.GO, KEGG enrichment analysis was performed on the Metascape platform to explore the mechanisms of the granules for treating LEAD of T2DM, and the Components-Targets-Pathways network was constructed. Last but not the least, molecular docking using AutoDockTools 1.5.6 was performed to verify the reactivity between drug active ingredients and disease targets. Results In the study, 71 active components with 261 potential targets of Zhige Tongmai Granules and 107 intersectional targets with DLEAD were obtained. Core components detected included quercetin, luteolin, kaempferol, formononetin, isorhamnetin, anhydroicaritin, diosgenin, beta-sitosterol, chrysocerin, and stigmasterol,and key targets included AKT1, IL-6, TNF, TP53, VEGFA, and IL-1B. There were 183 related pathways, including MAPK, and AGE-RAGE, HIF-1 signal pathways in complications of diabetes. Molecular docking results showed that TCM components combined with disease targets well. Conclusion Zhige Tongmai Granules could effectively treat DLEAD by acting with key targets(AKT1, IL-6, TNF, TP53, VEGFA, IL-1B) and regulating pathways(MAPK,AGE-RAGE, HIF-1 signal pathways) together, via core components of quercetin, luteolin, kaempferol, formononetin,isorhamnetin, anhydroicaritin, diosgenin, beta-sitosterol, chrysocerin, and stigmasterol.更多还原