基于PPAR信号通路探讨二陈汤对肥胖型CUMS小鼠的影响及作用机制OA

Objective:To observe the therapeutic effect of Erchentang on depression in obese mice and explore the therapeutic mechanism.Methods:C57BL/6J mice were randomized into the control,model,metformin(0.65 g·kg-1),and low-,medium-,and high-dose(3.35,6.7,and 13.4 g·kg-1,respectively)Erchentang groups.Gavage was initiated simultaneously with modeling and continued for 28 days.The therapeutic effects of Erchentang were evaluated through behavioral tests,liver and brain indices,liver function,lipid indicators,and histopathological changes in the liver and brain tissue.RNA-seq technology was used to conduct transcriptomic analysis of mouse liver tissue,and differentially expressed genes were screened and subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Key genes were further verified by Western blot and Real-time polymerase chain reaction(Real-time PCR).Results:Behavioral tests,liver function,lipid indicators,and histopathological changes in the liver and brain tissue all demonstrated that Erchentang had therapeutic effects on depression in obese mice.KEGG pathway enrichment analysis of transcriptomic data indicated that Erchentang treated depression in obese mice mainly through the peroxisome proliferator-activated receptor(PPAR)signaling pathway.Western blot and Real-time PCR results showed that compared with the model group,the low-,medium-,and high-dose Erchentang groups exhibited downregulated expression of fatty acid-binding protein(FABP)1(P<0.01)and upregulated expression of acyl-CoA oxidase(ACOX)1,PPARα,cholesterol 7α-hydroxylase(CYP7A)1,and phosphoenolpyruvate carboxy kinase(PCK)1(P<0.05)in the liver tissue.Conclusion:Erchentang exerts therapeutic effects on obesity-associated depression by regulating the PPAR signaling pathway and the expression of related genes FABP1,ACOX1,PPARα,CYP7A1,and PCK1.