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基于数据挖掘与网络药理学探讨中医外用药治疗糖尿病足溃疡的分子生物学机制
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Abstract:
目的：挖掘中医外用药治疗糖尿病足溃疡的用药规律，分析相关的药物靶点及疾病通路，探索核心组方的潜在作用机制。方法：对中国知网、万方、维普、中国生物医学文献、Pubmed等数据库中有关中药外用治疗糖尿病足溃疡的临床文献进行检索，通过IBM SPSS Modeler 18.0及IBM SPSS Statistics 26.0软件进行关联规则及聚类分析。利用TCMSP、SymMap、DisGenet、Genecards、TTD、OMIM、DrugBank等数据库及Cytoscape、DAVID软件进行网络药理学分析。结果：共筛选出164篇文献，148首外用处方，高频药物前6位依次为黄柏、当归、冰片、血竭、白芷和紫草。中药药性以寒、温为主，药味以辛、苦、甘味为主，归经以肝、脾经为主。178味中药关联分析得到4组关联药物，高频药物聚类分析得到2类组合。核心药物组合治疗糖尿病足溃疡的主要成分为槲皮素、棕榈酸、山达海松酸等，核心靶点为ESR1、EGFR、IL6等；主要信号通路包括PI3K-Akt、AGE-RAGE、MAPK等。结论：活血化瘀、清热补虚是中医外用方药治疗糖尿病足溃疡的基本法则，用药多为活血化瘀类药物与清热药、补虚药配伍使用，同时通过使用冰片等天然经皮吸收促透剂、提高外用药物使用剂量来增加皮肤对药物的吸收；数据挖掘得到的药对组合可为糖尿病足溃疡的临床选方用药提供参考；现代生物学机制可能与减轻炎症反应、促进血管新生等相关。
Objective: To explore the medication rule of external medicine in treating diabetes foot ulcers, analyze related drug targets and disease pathways, and explore the potential mechanism of core prescriptions. Methods: The clinical literature on the treatment of diabetes foot ulcers with external use of traditional Chinese medicine in the databases of CNKI, Wanfang, VIP, Chinese biomedical literature, Pubmed, etc. were searched, and the association rules and cluster analysis were carried out through IBM SPSS Modeler 18.0 and IBM SPSS Statistics 26.0 software. Perform network pharmacology analysis using databases such as TCMSP, SymMap, DisGenet, Genecards, TTD, OMIM, DrugBank, as well as Cytoscape and DAVID software. Result: A total of 164 articles and 148 topical prescriptions were screened, and the top 6 high-frequency drugs were Huangbai, Danggui, Borneol, Xuejie, Baizhi, and Zicao. The medicinal properties of traditional Chinese medicine are mainly cold and warm, and the medicinal flavors are mainly spicy, bitter, and sweet. The meridian tropism is mainly based on the liver and spleen meridians. Association analysis of 178 traditional Chinese medicines resulted in 4 groups of associated drugs, and high-frequency drug clustering analysis resulted in 2 combinations. The main components of the core drug combination for the treatment of diabetes foot ulcers are quercetin, palmitic acid, sandamaric acid, etc. The core targets are ESR1, EGFR, IL6, etc. The main signaling pathways include PI3K Akt, AGE-RAGE, MAPK, etc. Conclusion: Activating blood circulation and removing blood stasis, clearing heat and tonifying deficiency are the basic principles of Chinese medicine for external use in the treatment of diabetes foot ulcers. Most drugs are used in combination with drugs for activating blood circulation and removing blood
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