基于网络药理学和实验验证的小檗碱调控2型糖尿病大鼠脂肪沉积的作用及机制研究OA

Based on network pharmacology and molecular docking,combined with in vivo experiments,this study investigated the regulatory effects and mechanisms of berberine(BBR)on adipose deposition in rats with type 2 diabetes mellitus(T2DM).BBR targets were retrieved from the TCMSP database,while T2DM-related gene targets were obtained from TTD and GeneCards databases.Core targets were identified through protein-protein interaction(PPI)network analysis,and"active component-target-pathway"network was constructed by GO and KEGG pathway enrichment analysis then validated by molec-ular docking.A T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozoto-cin.Rats were randomly divided into six groups(n=10 per group):blank control,model,metformin(200 mg/kg),low-dose BBR(50 mg/kg),medium-dose BBR(100 mg/kg),and high-dose BBR(200 mg/kg).Fasting blood glucose(FBG)was measured periodically;serum fasting insulin(FINS)and glycated hemoglobin(GHb)were determined using ELISA;serum total cholesterol(TC),triglycerides(TG),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured with an automatic biochemical analyzer.HE staining was used to observe adipose tissue morphology,and Oil Red O staining to assess hepatic lipid deposition.Western blot and immunohistochemistry(IHC)were employed to determine the lo-calization and expression of proteins regulating adipose deposition.Network pharmacology identified 105 active components of BBR and 99 overlapping targets with T2DM.GO and KEGG enrichment analyses revealed pathways mainly involving transient receptor potential(TRP)channels mediated by inflammation,neuroactive ligand-receptor interaction,endocrine resistance,and vascular endothelial growth factor(VEGF)signaling.Molecular docking indicated favorable binding activity between key BBR components and core targets.In vivo results demonstrated that BBR treatment at different doses effectively alleviated in-sulin resistance,reduced serum FBG,GHb,TG,TC,ALT,and AST levels(P＜0.01),preserved adipose tissue morphology,and improved hepatic lipid deposition.Western blot and IHC analyses showed that medium-dose BBR downregulated fatty acid synthetase(FAS),peroxisome proliferator-activated receptor gamma(PPARγ),CCAAT/enhancer-binding protein alpha(C/EBPα),β3-adrenoceptor(β3-AR),peroxisome proliferator-activated receptor-γ coactivator-1 α(PGC1α),and uncoupling protein 1(UCP1)(P＜0.01),while upregulating hormone-sensitive lipase(HSL)and adipose triglyceride lipase(ATGL)expression(P＜0.01).These findings suggest that BBR alleviates insulin resistance and reduces adipose deposition in T2DM rats by regulating the β3-AR signaling pathway.