基于网络药理学和分子对接及动物实验探讨毛蕊花糖苷治疗糖尿病肾脏病的作用机制OA北大核心

Objective:Based on network pharmacology,molecular docking,and animal experiments,this study aims to ex-plore the key target and potential molecular mechanism of acteoside treatment in Diabetic Kidney Disease(DKD).Methods:Po-tential target genes of acteoside were obtained from Swiss Target Prediction,GeneCards,TargetNet,SuperPred,SEA,and Pharmmapper databases;potential target genes of DKD were obtained from GeneCards,OMIM,DrugBank,and TTD databas-es.Common target genes were imported into the STRING database to obtain protein-protein interaction relationships and con-struct a protein interaction network using Cytoscape software.GO and KEGG enrichment analysis were performed using Metascape database.Molecular docking of acteoside with core target genes was performed using the CB-Dock2 website.A DKD rat model was established,and the effects of acteoside on DKD rat kidney pathology and function were observed through HE,PAS,TEM,and biochemical index detection.The impact of acteoside on the expression of inflammatory factors and key path-ways was also verified.Results:A total of 469 potential targets for acteoside and 1 073 potential targets for DKD were obtained.65 potential target genes were identified for acteoside in treating DKD,with 441 biological processes and 153 signal pathways.GO and KEGG analyses indicated that acteoside may exert its therapeutic effect on DKD by regulating the expression of inflammatory factors related to the NF-κB signaling pathway.Molecular docking results showed that acteoside could spontaneously bind to key targets such as TP53,CASP3,MMP9,STAT3,NFKB1,and PTGS2 with binding energies<-5 kJ/mol.Animal experi-ments demonstrated that compared to the DKD group,acteoside could improve rat kidney pathology,reduce blood urea nitrogen,blood creatinine,and 24 h-UPro levels(P<0.05),decrease serum levels of TNF-α,IL-6,and IL-1β(P<0.05),and reduce p-P65 protein expression(P<0.05).Conclusion:Acteoside can effectively improve renal function and kidney pathology in DKD rats,reduce levels of pro-inflammatory cytokines,and its mechanism may be related to the inhibition of the NF-κB signaling path-way.