【摘要】 目的 探讨西帕依固龈液治疗糖尿病足溃疡（DFU）可能的药效成分及作用的靶点和机制。方法 取雄性SD大鼠40只，以高脂乳剂灌胃（每100 g体质量0.6 mL，每天1次，连续30 d）后，腹腔注射1%链脲佐菌素（60 mg/kg，每天1次，连续3 d），复合饱和氢氧化钠溶液腐蚀足部皮肤以复制DFU大鼠模型。26只建模成功大鼠随机分为模型组和给药组，各13只。另取10只大鼠设为空白组。治疗1,7,15 d测量大鼠溃疡面积，计算溃疡抑制率；酶联免疫吸附法检测血清表皮生长因子（EGF）含量；显微镜下观察大鼠溃疡组织形态。通过文献检索并利用中药系统药理学数据库和分析平台（TCMSP）获取西帕依固龈液的活性成分及作用靶点，运用人类基因组数据库（Genecards）、药物数据库（DrugBank）、人类孟德尔遗传数据库（OMIM）和治疗靶点数据库（TTD）获取DFU相关靶点，获取药物-疾病的交集靶点，构建“成分-靶点”网络、蛋白相互作用（PPI）网络拓扑分析图，进行基因本体论（GO）功能富集和京都基因与基因组百科全书（KEGG）通路富集分析；对核心成分与核心靶点进行分子对接验证。结果 给药7,15 d后，给药组大鼠溃疡面积明显小于模型组（P <0.05），给药15 d时给药组溃疡抑制率为58.38%；与模型组比较，给药组EGF含量明显升高（P <0.05），可见毛囊再生，脂肪细胞增多。西帕依固龈液治疗DFU可能的有效成分有6个，主要为鞣花酸、没食子酸、没食子酸甲酯等；PPI网络包括29个交集靶点，平均Degree值9.66，获得9个中心节点，主要有TP53,VEGFA,CASP3等；富集分析结果表明，西帕依固龈液治疗DFU的靶点主要参与NF-κB及PI3K-Akt等信号通路；核心成分与核心靶点的结合能均小于0 kcal/mol。结论 西帕依固龈液对DFU有一定抑制作用，可能通过多成分-多靶点-多通路共同作用实现。更多还原

【Abstract】 Objective To investigate the possible pharmacodynamic components,targets and mechanisms of Xipayi Mouth Rinse in the treatment of diabetic foot ulcer(DFU).Methods Forty male SD rats were selected and given intragastric administration of high-fat emulsion(0. 6 mL/100 g,once a day for 30 d),and then they were intraperitoneal injection of 1% streptozotocin(60 mg/kg,once a day for 3 d),and then their foot skin was corroded by saturated sodium hydroxide solution to establish the DFU model rats. A total of 26 successfully modeled rats were randomly divided into the model group and the administration group,with 13 rats in each group. Another 10 rats were selected as the blank group. The area of ulcer was measured and the inhibition rate of ulcer was calculated after 1,7 and 15 d of administration. The content of serum epidermal growth factor(EGF) was detected by the enzyme-linked immunosorbent assay(ELISA). The morphology of ulcer tissue was observed under microscope. The active components and action targets of Xipayi Mouth Rinse were obtained by literature retrieval and Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP), and DFU-related targets and drug-disease intersection targets were obtained by the Genecards,DrugBank,Online Mendelian Inheritance in Man(OMIM) and Therapeutic Target Database(TTD) to construct a ″component-target″ network,topological graph of protein-protein interaction(PPI) network. Gene Ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out.The key components were verified by molecular docking with the key targets.Results On the 7th and 15th day of administration,the area of ulcer in the administration group was significantly smaller than that in the model group(P < 0. 05),and the inhibition rate of ulcer in the administration group was 58. 38% on the 15th day of administration. Compared with those in the model group,the content of EGF in the administration group significantly increased(P < 0. 05),the hair follicle regeneration and adipocyte proliferation were observed in the administration group. There were six possible active components of Xipayi Mouth Rinse in the treatment of DFU,mainly including ellagic acid,gallic acid,methyl gallate,etc. PPI network included 29 intersection targets,with an average Degree of 9. 66. Nine central nodes were obtained,mainly including TP53,VEGFA,CASP3,etc. Enrichment analysis showed that the target of Xipayi Mouth Rinse in the treatment of DFU mainly participated in the NF-κB and PI3K-Akt and other signaling pathways. The binding energies of key components and key targets were less than 0 kcal/mol.Conclusion Xipayi Mouth Rinse has a certain inhibitory effect on DFU,which may be realized through the combined action of multiple components,multiple targets and multiple pathways.更多还原