摘要
目的:探讨尿毒清颗粒治疗糖尿病肾病的潜在机制.方法:利用TCMSP数据库及文献收集筛选UCG活性成分及作用靶点,通过TTD、OMIM、GeneCards、drugbank及DisGeNET平台筛选DN相关靶点,并与UCG作用靶点取交集;通过STRING平台获得蛋白互作关系,借Cytoscape3.8.0可视化并分析提取UCG治疗DN的关键靶点;通过DAVID 6.8进行GO和KEGG富集分析;运用AutoDock Tools和Pymol对主要活性成分与关键靶点进行分子对接验证.结果:共获得UCG活性成分248个,其中主要活性成分有槲皮素、木犀草素、β-谷甾醇、山奈酚等,DN潜在靶点1 813个,二者交集靶点156个,网络拓扑分析获得17个关键靶点,选取JUN、SRC、MAPK1作为核心靶点.GO功能富集分析的生物过程主要涉及细胞对信号转导、活性氧的调控、凋亡过程的调控等;KEGG通路富集分析包括流体剪切应力与动脉粥样硬化、AGE-RAGE信号转导通路、TNF信号通路、Toll样受体信号通路、MAPK信号通路等.分子对接结果显示,槲皮素、木犀草素、β-谷甾醇、山奈酚与3个核心靶点均具有较好的结合活性.结论:UCG可能通过槲皮素、木犀草素、β-谷甾醇、山奈酚等多种活性成分作用于多个靶点,参与调节多信号通路,发挥抗炎、抗氧化应激、抑制细胞凋亡等作用,发挥保护肾功能治疗DN的作用.
Abstract
Objective:To investigate the potential mechanism of uremic clearance granules in the treatment of diabetic nephropathy.Methods:The active components and targets of Uremic clearance granule were screened by TCMSP database and literature collection.The targets related to diabetic nephropathy were screened by TTD,OMIM,GeneCards,drugbank and DisGeNET platforms,and the intersection with the targets of Uremic clearance granulewas taken.The protein interaction was obtained through STRING platform,and the key targets for the treatment of diabetic nephropathy were visualized and analyzed by Cytoscape 3.8.0.GO andKEGG enrichment analysis was performed by DAVID 6.8.AutoDock Tools and Pymol were used to verify the molecular docking of the main active ingredients and key targets.Results:A total of 248 active components of Uremic clearance granule were obtained,of which the main active components were quercetin,luteolin,β-sitosterol and kaempferol.There were 1813 potential targets for diabetic nephropathy,and 156 intersection targets.Seventeen key targets were obtained by network topology analysis,and JUN,SRC and MAPK1 were selected as the core targets.The biological process of GO functional enrichment analysis mainly involves the regulation of signal transduction,reactive oxygen species and apoptosis.KEGG pathway enrichment analysis included fluid shear stress and atherosclerosis,AGE-RAGE signal transduction pathway,TNF signal pathway,Toll-like receptor signal pathway,MAPK signal path way,etc.Molecular docking results showed that quercetin,luteolin,β-sitosterol and kaempferol had good binding activity with the three core targets.Conclusion:Uremic clearance granule may act on multiple targets through quercetin,luteolin,β-sitosterol,kaempferol and other active ingredients,participate in regulating multiple signaling pathways,play anti-inflammatory,anti-oxidative stress,inhibition of apoptosis,and play a role in protecting renal function in the treatment of DN.
维普
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