Study on vaccarin in improving intestinal flora disorder and renal lipid deposition in diabetes nephropathy mice
OBJECTIVE To study the effect of vaccarin(Vac)on renal lipid synthesis in diabetes nephropathy mice and its mechanism.METHODS The diabetic nephropathy(DN)mice model was established by feeding high-fat diet and intraperitoneal injection of streptozocin.The mice were randomly divided into three groups:normal group,diabetes nephropathy model group and Vac treatment group.A glucometer was used to detect fasting blood glucose in mice.The kits were used to detect urea nitrogen,urinary creatinine,24 h urinary protein and urinary protein creatinine levels in urine,blood creatinine,triglyceride,total cholesterol,low-density lipoprotein,and high-density lipoprotein levels in serum,and triglyceride and total cholesterol levels in kidney tissue.HE and PAS staining were used to evaluate the pathological changes of mouse kidney.TBA kit was used to determine the content of total bile acid in serum of mice.The mRNA expression of sterol-regulatory element binding protein 1 and fatty acid synthase was detected by real-time fluorescence quantitative PCR.The mRNA and protein expression levels of farnesol X receptor(FXR)and G protein coupled bile acid receptor 5(TGR5)in mouse kidney tissues were detected by real-time fluorescent quantitative PCR,immunoblotting and immunohistochemistry,respectively.RESULTS Compared with the normal group,DN mice had higher blood glucose and blood lipid,increased renal lipid deposition,and impaired renal function.After treatment with Vac,Vac could alleviate lipid metabolism disorder and improve renal function in DN mice.The intestinal flora of DN mice was disordered,and the beneficial bacteria at the level of phylum and genus decreased,while the harmful bacteria increased.The intervention of Vac could significantly improve this situation.At the same time,Spearman correlation analysis also showed that the level of lipid metabolism in mice was significantly related to the intestinal flora.Compared with the normal group,the content of total bile acid in serum of the model group mice increased,and the expression of bile acid receptor FXR and TGR5 receptor decreased significantly.Vac could reduce the content of total bile acid and up regulate the expression of FXR and TGR5 receptor.CONCLUSION Vac can alleviate lipid deposition and improve renal function in DN mice by regulating the composition of intestinal flora and its metabolite bile acid.These results suggest that Vac may be an effective drug candidate to improve renal lipid deposition in patients with DN.
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