基于网络药理学和高糖诱导H9c2细胞模型探讨鹿茸多肽改善糖尿病心肌病作用机制OA

Objective To explore the mechanism by which velvet antler polypeptides(VAP)ameliorate diabetic cardiomyopathy(DCM)using network pharmacology and a high glucose-induced H9c2 cell model.Methods VAP targets were retrieved from the Similarity Ensemble Approach database,and DCM-related genes were obtained from GeneCards,OMIM,and the Comparative Toxicogenomics Database.Intersecting targets were identified using the Venny 2.1.0 platform,and their protein-protein interaction network relationships were analyzed using the STRING database and Cytoscape 3.8.2 to screen for core targets.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the DAVID database.A high glucose-induced H9c2 cell injury model was established to evaluate the effects of VAP and the expression of proteins in the sirtuin 1(SIRT1)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Results Screening identified 374 VAP targets,3 783 DCM-related genes,and 179 intersecting targets.Ten core targets,including interleukin-1β(IL1β),matrix metalloproteinase-9(MMP9),and STAT3,were identified.Enrichment analyses indicated VAP may exert therapeutic effects through pathways including the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,apoptosis,and other cancer-related signaling pathways.In vitro,VAP can alleviate the high glucose-induced reduction in H9c2 cell viability(P<0.05,P<0.01),restored mitochondrial membrane potential,reduced reactive oxygen species levels,increased ATP levels and the nicotinamide adenine dinucleotide(NAD+)/nicotinamide adenine dinucleotide reduced(NADH)ratio(P<0.01),and upregulated the protein expression of SIRT1 and phosphorylated-STAT3(P<0.01).Conclusions VAP effectively attenuated high glucose-induced mitochondrial dysfunction and oxidative stress in H9c2 cells,potentially through regulation of the SIRT1/STAT3 signaling pathway.