首页|降糖甲治疗2型糖尿病的机制研究

降糖甲治疗2型糖尿病的机制研究

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基于生物信息学、网络药理学和分子对接技术探讨降糖甲颗粒(JTJ)治疗2型糖尿病(T2DM)的作用机制.通过TCMSP、Uniprot数据库、swisstarget和SEA数据库筛选降糖甲颗粒的活性化合物和作用靶点,从GEO数据库获取T2DM患者组胰岛样本和非T2DM患者组胰岛样本数据,利用R语言limma包筛选差异表达基因,二者取交集得到JTJ-T2DM共有靶点.通过Cytoscape3.9.1绘制JTJ-T2DM-靶点网络图,利用STRING数据库、Cytoscape3.9.1的cytoHubb插件制作JTJ-T2DM共有靶点的PPI网络图并获取关键靶点(Hubs).利用DAVID平台对JTJ-T2DM共有靶点进行GO功能富集分析及KEGG通路富集分析,对共有靶点有差异表达并进行ROC分析,最后通过DS BIOVIA软件进行分子对接验证.结果显示,最终获得41个JTJ活性化合物,909个药物作用靶点,2952个T2DM靶点,JTJ-T2DM交集靶点160个,Hubs 12个;GO及KEGG富集分析结果显示,JTJ主要参与细胞凋亡等过程,调控MAPK及AGE-RAGE等信号通路而治疗T2DM;差异表达结果显示,MAPK14、PRKCZ、PTPN11具有显著差异表达且诊断价值高;分子对接结果显示(+)-丁香树脂醇-O-β-D-葡萄糖苷与LCK和PTPN11亲和力最强,蒙花苷与PRKCZ亲和力最强.本研究初步揭示了降糖甲颗粒治疗2型糖尿病的作用机制,为其治疗2型糖尿病提供充分、可靠的理论依据.
Mechanism of Jiangtangjia granules in the treatment of diabetes mellitus type 2
Based on bioinformatics,network pharmacology and molecular docking,this paper explores the action mechanism of Jiangtangjia granules(JTJ)in the treatment of diabetes mellitus type 2(T2DM).The active com-pounds and action targets of JTJ were screened out by using TCMSP,Uniprot,swisstarget and SEA databases,and the data of pancreas islet samples from T2DM patients and non-T2DM patients were obtained from GEO database.The differentially expressed genes were screened out by using R language limma package,and the JTJ-T2DM com-mon targets were obtained.The JTJ-T2DM-target network map was drawn by Cytoscape 3.9.1,and the PPI net-work map of JTJ-T2DM common targets was produced and the key targets(Hubs)were obtained by using STRING database and cytoHubb plugin of Cytoscape 3.9.1.The DAVID platform was used to perform GO functional enrich-ment analysis and KEGG pathway enrichment analysis on JTJ-T2DM common targets.Differential expression of the common targets and ROC analysis were performed.Finally,molecular docking was carried out by using DS BIOVIA software.The results showed that 41 JTJ active compounds,909 drug targets,2952 T2DM targets,160 JTJ-T2DM crossover targets,and 12 Hubs were obtained.The results of GO and KEGG enrichment analysis showed that JTJ mainly involved in apoptosis and regulated MAPK,AGE-RAGE and other signaling pathways to treat T2DM.Dif-ferential expression results showed that MAPK14,PRKCZ and PTPN11 were significantly differentially expressed and had high diagnostic value.Molecular docking results showed that(+)-syringaresinol-O-beta-D-glucoside had the strongest affinity with LCK and PTPN11,and linarin had the strongest affinity with PRKCZ.This study has pre-liminarily revealed the action mechanism of Jiangtangjia granules in the treatment of diabetes mellitus type 2,and has provided a sufficient and reliable theoretical basis for its treatment of diabetes mellitus type 2.

Jiangtangjia granules(JTJ)diabetes mellitus type 2action mechanism

程方玲、田昌林、张楠楠

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贵州中医药大学 药学院,贵州 贵阳 550025

贵州中医药大学 基础医学院,贵州 贵阳 550025

降糖甲颗粒 2型糖尿病 作用机制

贵州省卫生健康委科学技术基金贵州中医药大学博士启动金

gzwkj2022-008[2021]10号

2024

贵州科学
贵州科学院

贵州科学

影响因子:0.395
ISSN:1003-6563
年,卷(期):2024.42(1)
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