基于网络药理学结合GEO数据集探讨白术治疗2型糖尿病的分子机制

Study on the molecular mechanism of Atractylodes macrocephala in the treatment of type 2 diabetes mellitus based on network pharmacology and GEO datasets

目的基于网络药理学及GEO数据集初步探索白术防治2型糖尿病的分子机制。方法根据标准流程对GEO数据库中基因芯片数据(GSE7014)进行收集处理、整合,对芯片数据进行归一化校正,用已编制好的R语言程序进行差异基因分析。通过TCMSP数据库下载白术化学成分,基于Swiss Target Prediction筛选化学成分靶点,通过FunRich软件获得白术治疗2型糖尿病的靶点,对其靶点进行生物信息学分析。结果白术55个化学成分通过Swiss Target Prediction数据库获得262个靶点。通过GEO数据库筛选2型糖尿病差异基因699个,通过FunRich软件取交集,共筛选出13个差异基因,主要参与胰岛素抵抗和MAPK信号通路(P<0.01且P_(adjust)<0.01),通过化学成分-靶点-通路网络模型,明确白术防治2型糖尿病的关键靶点为蛋白激酶C-θ、核糖体蛋白S6激酶α3、转录因子p65、Ras鸟苷酸释放蛋白3、电压依赖性钙通道δ1亚单位。白术防治2型糖尿病的主要成分为挥发油、倍半萜内酯、氨基酸和多炔类化合物。结论筛选出的通路及差异基因有助于加深对2型糖尿病发病分子机制的理解,为2型糖尿病药物的开发及应用提供依据。

Objective To preliminarily explored the molecular mechanism of Atractylodes macrocephala(AM) in the prevention and treatment of type 2 diabetes(T2DM) based on network pharmacology and GEO datasets.Methods According to the standard flow,the chip data(GSE7014) in GEO database were collected and processed,integrated,the chip data was normalized and corrected,and differential gene was analyzed with the prepared R language program.The chemical constituents of AM were downloaded from TCMSP database,and targets of chemical constituents were screened using Swiss Target Prediction platform.The targets of AM for T2DM were obtained base on FunRich software and analyzed in bioinformatics.Results 262 targets were obtained for the 55 chemical constituents of AM through the Swiss Target Prediction database.699 different genes of T2DM were screened out by using GEO database and 13 different genes by using funrich software.It mainly involves insulin resistance and MAPK signaling pathway(P<0.01 and P_(adjust)<0.01).The key targets of AM for the prevention and treatment of T2 DM are Protein kinase C theta type,ribosomal protein S6 kinase alpha-3,transcription factor p65,ras guanyl nucleotide releasing protein 3,voltage-dependent calcium channel subunit delta-1 based on chemical composition-target-pathway network model.Volatile oil,sesquiterpene lactone compounds,amino acids,polyacetylene compounds are the main components of AM for the prevention and treatment of T2DM.Conclusion The screened pathways and differential genes deepen the understanding of the molecular mechanism of T2 DM,and provide a basis for the development and application of drugs for T2DM.