Studies On The Mechanism Of YiZhiRen In The Treatment Of Diabetic Nephropathy Based On Gut Microbiota And Metabonomics Analysis

Objective:The pathogenesis of diabetic nephropathy?DN?is diverse and complex,it also be considered as one of the fatal factors in patients.So it is urgent to understand the pathogenesis of DN and provide a new direction for the treatment of it.Based on the analysis of gut microbiota and metabolome,this study shows the therapeutic effect of Yizhiren on DN.Methods:Mice were divided into DB-/DB-S,db-/db-YZR,db-/db-S and db-/db-IRB groups.Physiological and biochemical parameters were measured weekly,including:blood glucose concentration,urea nitrogen,Urinary creatinine,urinary albumin and mouse body weight were sacrificed after 8 weeks of feeding.The histopathological changes of renal sections after HE staining and serum oxidative stress such as catalase,glutathione and malondialdehyde were measured too.The db-/db-YZR and db-/db-S mouse feces were collected,and the different expression of metabolomics and gut microbiota between the model group and the Yirenren model group were detected,analyzed and compared based on LC-MS technology and 16sRNA high-throughput sequencing technology.Results:There was no significant difference in body weight between db-/db-S and db-/db-YZR and db-/db-IRB;compared with db-/db-S,db-/db-YZR and db-/db-IRB can reduce blood glucose concentration,urea nitrogen content?P<0.05?,urine creatinine content?P<0.05?,urinary albumin content?P<0.05?;compared with db-/db-S,db-/db-YZR and db-/db-IRB can significantly reduce H₂O₂content,SOD inhibition rate,MDA content and O^2-activity?P<0.05?,elevated CAT activity and T-GSH content?P<0.05?,and can significantly improve renal pathological status.Compared with the metabolites of db-/db-YZR and db-/db-S,the enrichment is related to the metabolic pathways that may affect DN in Yizhiren:glycerophospholipid metabolism,sphingolipid metabolism,autophagy,glycosylation Phosphatidylinositol?GPI?-anchor biosynthesis.In the identification of intestinal microbes,db-/db-YZR and db-/db-S specifically differentiated from the gut microbiota by 19 genus,8 families and 3 phylum.Conclusion:This study demonstrates that Yizhiren can reduce blood sugar,urea nitrogen,urinary albumin,urinary creatinine,inhibit oxidative stress and improve renal pathological status in mice with DN,and also regulate metabolomics and intestinal tract.The function of microorganisms to achieve the purpose of treating DN.