Study on the protective mechanism of Yizhiren regulating lipid metabolism in mice with diabetic nephropathy

Objective:To study the protective mechanism of Yizhiren on the diabetic nephropathy(DN)mouse model based on network pharmacology and metabolomics.Methods:Urea nitrogen,urinary creatinine,urinary albumin were detected in each group of mice,and pathological sections of mice kidney were observed.TCMSP database was used to search for the components and targets of Yizhiren,GeneCards database was used to search for DN-related genes,and drug-component-target-disease network and KEGG signaling pathway were constructed.The fecal samples of mice in the Yizhiren group and the Saline group were collected,metabolomics techniques were used to screen different metabolites,and potential metabolic pathways were analyzed using KEGG database.Results:Compared with the model group,Yizhiren significantly reduced the levels of urea nitrogen,urinary creatinine and urinary albumin in DN mice(P<0.05 or P<0.01),and improved the renal pathology of mice.It was predicted that Yizhiren had 4 effective components and 28 potential targets for treating DN.The KEGG enriched 43 signal pathways,and the main metabolic pathway was lipid metabolism.A total of 584 different metabolites were screened from feces of the two groups(P<0.05).The main metabolic pathways were lipid metabolism,namely sphingolipid metabolism and glycerol phospholipid metabolism,among which the metabolites contained mainly sphingolipin,phosphatidylcholine,lysophosphatidylcholine and phosphatidylethanolamine.Compared with the normal saline group,these four metabolites in Yizhiren decreased significantly(P<0.01 or P<0.001).Conclusion:The protective mechanism of Yizhiren in DN mice may be related to the regulation of sphingolipid metabolism,glycerol phospholipid metabolism and the disorder of its metabolites.