Protective Effect And Intervention Mechanism Of Saxagliptin On Kidney Injury In Diabetic Rats

Objective:To explore the protective effect of saxagliptin on kidney of diabetic rats and its potential therapeutic mechanism.Methods:15 SD male rats were given high-fat and high-sugar diet combined with peritoneal injection of streptozotocin(STZ)induced to establish the type 2 diabetes mellitus(T2DM)model,and then were randomly divided into T2DM group and Sax group after the model was successfully established;6 rats were selected as normal control(NC)group randomly.The rats of Sax group were given the saxagliptin solution.The rats of NC and T2DM groups were injected with the same amount of sodium carboxymethyl cellulose solution.After 8 weeks of continuous gastric administration,the rats were sacrificed and their blood and kidney tissues were collected.Glucose(Glu),aspartate transaminase(AST),alanine transaminase(ALT),serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),serum total cholesterol(TC),triglycerides(TG)were detected by automatic biochemical analyzer.HE,PAS,Masson staining and transmission electron microscopy were performed to observe the morphological changes of renal.The expression levels of mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),interleukin 1(IL-1),interleukin 6(IL-6)and tumor necrosis factor(TNF-α)in renal rats in each group were quantitatively determined by Western Blot assay.Immunohistochemical staining was used to detect the protein expression level of mammalian target of rapamycin(mTOR),interleukin 1(IL-1),IL-6,tumor necrosis factor α(TNF-α)in renal tissues.Results:Compared with the NC group,the levels of biochemical indicators such as Glu、AST、ALT、Scr、BUN、UA、TC and TG showed significant increase;the number of glomerular mesangial cells also increased,and the mesangial matrix hyperplasia,mTOR,IL-1,IL6,TNF-α protein expression levels exhibited significant increase in T2DM group.Compared with T2DM group,Sax group showed decreased levels of biochemical indicators such as Glu、AST、ALT、Scr、BUN、UA、TC and TG and improved renal pathological damage performance together with a profound reduction in mTOR,IL-1,IL-6,TNF-α protein expression level.Conclusion:Saxagliptin may suppress inflammatory response and reduce renal injury in diabetic rats by down-regulating mTOR expression.