西帕依固龈液治疗糖尿病足溃疡效果及网络药理学分析  

Efficacy of Xipayi Mouth Rinse on Diabetic Foot Ulcer Based on the Network Pharmacology

作　　者：李茜 郝梦[1] 李金耀 李建德[4] 刘婷 季志红 LI Qian;HAO Meng;LI Jinyao;LI Jiande;LIU Ting;JI Zhihong(Xinqikang Pharmaceutical Co.,Ltd.,Urumqi,Xinjiang,China 830011;School of Life Science and Technology,Xinjiang University,Urumqi,Xinjiang,China 830049;The Fourth Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,China 830054;Xinjiang Qimu Pharmaceutical Research Institute,Urumqi,Xinjiang,China 830011;Xinjiang Key Laboratory of Traditional Chinese MedicinePharmaceutical Common Key Technology Research,Urumqi,Xinjiang,China 830011)

机构地区：[1]新奇康药业股份有限公司,新疆乌鲁木齐830011 [2]新疆大学生命科学与技术学院,新疆乌鲁木齐830049 [3]新疆医科大学第四附属医院,新疆乌鲁木齐830054 [4]新疆奇沐医药研究院,新疆乌鲁木齐830011 [5]新疆中药<民族药>制药共性关键技术研究重点实验室,新疆乌鲁木齐830011

出　　处：《中国药业》2023年第2期48-55,共8页China Pharmaceuticals

基　　金：中国民族医药学会经典名方及大品种培育分会科研项目[PZ2020-04]。

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。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 foll

关 键 词：西帕依固龈液 糖尿病足溃疡 网络药理学 大鼠 动物实验 作用机制 

分 类 号：R965[医药卫生—药理学]