基于网络药理学和实验验证探讨三黄益肾胶囊治疗糖尿病的分子机制  

Exploration on the molecular mechanism of Sanhuang Yishen Capsules for the treatment of diabetes based on network pharmacology and experimental verification

作　　者：孟晓峰[1] 白海龙 边云[1] 张爱族 田风胜[1] 崔荣岗[1] 苏阳[1] 李娟[1] Meng Xiaofeng;Bai Hailong;Bian Yun;Zhang Aizu;Tian Fengsheng;Cui Ronggang;Su Yang;Li Juan(Department of Diabetes,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou 061000,China)

机构地区：[1]河北省沧州中西医结合医院糖尿病三科,沧州061000

出　　处：《国际中医中药杂志》2024年第10期1330-1337,共8页International Journal of Traditional Chinese Medicine

基　　金：河北省中医药管理局科研计划项目(2022511)。

摘　　要：目的通过网络药理学、分子对接和实验验证探讨三黄益肾胶囊治疗糖尿病的物质基础及潜在作用机制。方法利用中国天然产物化学成分数据库和SymMap数据库筛选三黄益肾胶囊的活性成分及作用靶点,通过GeneCards数据库筛选T2DM相关靶点,构建“中药-活性成分-靶点”网络,使用R语言对交集靶点进行GO功能及KEGG通路富集分析。选择关键活性成分与潜在核心靶点进行分子对接验证。将60只大鼠按随机数字表法分为正常组、模型组、磷酸西格列汀片组、三黄益肾胶囊组,每组15只。除正常组外,其余各组制备T2DM大鼠模型,灌胃相应药物8周。采用放射免疫分析法检测空腹血糖(FBG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR),Western blot法检测胰腺组织表皮生长因子受体(EGFR)、表皮生长因子(EGF)、AKT1、肿瘤抑制蛋白p53(TP53)、胱天蛋白酶3(CASP3)蛋白表达。结果得到三黄益肾胶囊活性成分160个,作用靶点298个,T2DM相关靶点2194个,三黄益肾胶囊与T2DM交集靶点166个。GO功能和KEGG通路富集分析得出主要涉及信号转导、氧化应激、细胞凋亡等生物学反应过程,主要参与P13K/Akt、P53和CASP3等靶点的调控。分子对接结果表明,筛选得到的主要活性成分与靶点有较强的结合能力。与模型组比较,三黄益肾胶囊组大鼠FBG、FINS、HOMA-IR、TP53、CASP3降低(P<0.05),EGFR、EGF、Akt1蛋白升高(P<0.05)。结论三黄益肾胶囊治疗糖尿病的作用机制可能与调节EGF/EGFR/P13K/Akt信号通路、TP53信号通路、CASP3信号通路、PPARG信号通路、ESR1信号通路、PTGS2信号通路、CAT信号通路和CTNNB1信号通路有关。Objective To explore the material basis and potential mechanism of Sanhuang Yishen Capsules in the treatment of diabetes through network pharmacology,molecular docking and experimental verification.Methods The active components and targets of Sanhuang Yishhen Capsules were screened using China Natural product chemical composition database and SymMap database,and the related targets of T2DM were screened by GeneCards database.The"Chinese materia medica-active component-target"network was constructed,and the intersection genes were enriched by GO and KEGG using R language.Key active components were selected for molecular docking verification with potential core targets.60 rats were divided into normal group,model group,and Sanhuang Yishen Capsules group according to random number table method,with 15 rats in each group.In addition to the normal group,the diabetic rat model was prepared in the other groups,and the corresponding drugs were intragastric in each group for 8 weeks.The levels of fasting blood glucose(FBG),fasting insulin(FINS)and insulin resistance index(HOMA-IR)were measured by radioimmunoassay.Western blotting was used to detect protein expressions of epidermal growth factor receptor(EGFR),epidermal growth factor(EGF),Akt serine/threonine kinase 1(AKT1),recombinant tumor protein p53(TP53),and recombinant caspase 3(CASP3).Results A total of 160 active components and 298 targets of Sanhuang Yishen Capsules,2194 targets related to T2DM,and 166 intersection targets were obtained.GO and KEGG analyzed a series of biological reaction processes mainly involved in signal transduction,oxidative stress,apoptosis,etc.,and mainly involved in the regulation of P13K/Akt,P53,CASP3 and other targets.The results of molecular docking showed that the main active components obtained by screening had strong binding with the target.Compared with model group,FBG,FINS,HOMA-IR,TP53 and CASP3 in Sanhuang Yishen Capsules group decreased(P<0.05),EGFR,EGF and Akt1 proteins increased(P<0.05).Conclusion The mechanism of Sanhuang Yish

关 键 词：糖尿病 2型 三黄益肾胶囊 网络药理学 表皮生长因子受体 丝氨酸/苏氨酸蛋白激酶1 肿瘤抑制蛋白p53 

分 类 号：R285[医药卫生—中药学]