基于网络药理学与实验验证探究金丝桃苷干预糖尿病肾病的作用机制OA

Objective:To investigate the potential mechanism of Hyperoside(Hyp)in the intervention of diabetic nephropathy(DKD)through network pharmacology and animal experiments.Methods:Target genes related to Hyp were predicted using the TCMSP and Uniprot databases.DKD-related target genes were obtained from the GAD database.The intersection network was constructed using PPI networks of Hyp and DKD targets,and core targets were screened based on Degree values.GO analysis of the targets for Hyp's protective effect on DKD was conducted using the DAVID database to predict the mechanism of Hyp in the intervention of diabetic nephropathy.Thirty-two male C57BL/6J mice at 8 weeks of age were randomly divided into a blank control group(N group,8 mice)fed with regular diet,and the remaining mice were used to establish DKD models using a high-fat diet combined with streptozotocin(STZ).Successfully modeled mice were randomly divided into a model group(M group),a Hyperoside group(H group,200 mg/(kg·d)),and a Rosuvastatin group(S group,5.2 mg/(kg·d)),with 8 mice in each group.Treatment was administered by gavage for 16 weeks,once daily.Immunohistochemistry and Western blotting were used to detect ERK1/2 signaling pathway-related proteins and downstream inflammatory factors to explore the mechanism of Hyp's intervention in DKD at the molecular level.Results:Network pharmacology analysis identified five core target proteins:TP53,ICAM-1,HSP90AA1,ESR1,and EGFR,and 20 biological processes and signaling pathways(P<0.05).The ERK1/2 signaling pathway was predicted to be one of the main pathways through which Hyp intervenes in DKD.Animal experiment results showed that compared with the model group,the expression of Ras,Raf,MEK,ERK1/2,and p-ERK1/2 proteins related to the Ras/Raf/MEK/ERK1/2 pathway was reduced in the kidneys of mice in the Hyperoside group.Additionally,the expression of downstream inflammatory factors NF-κB,TNF-α,MCP-1,and ICAM-1 was also significantly decreased,with statistically significant differences(P<0.01,P<0.05).Conclusion:Hyp can protect the kidneys and improve renal function by inhibiting the activation of the Ras/Raf/MEK/ERK1/2 signaling pathway and further suppressing the production of downstream inflammatory factors,thereby delaying the onset and progression of DKD.