Effect Of Sitagliptin On Renal Injury Induced By Streptozotocin In Type 1 Diabetic Mice And Its Mechanism

Object:To explore the effects and mechanisms of sitagliptin(SIT)on renal injuries in streptozotocin-induced type 1 diabetic mice.Methods:30 CD1 mice were randomly divided into normal control group(NC)and experiment group(EXP).The EXP group was intraperitoneally injected with streptozotocin(150 mg·kg-1)once and blood glucose ≥16.7 mmol·L-1 was considered as diabetes mellitus(DM).DM mice were randomly divided into two subgroups: diabetic group(DM)and SIT group(SIT).SIT group was treated with SIT(15 mg·kg-1·d-1)via intragastric administration for 4 weeks while the mice in DM group and NC group treated with equal volume of ultrapure water.At the end of the experiment,serum was used to detect urea nitrogen(BUN)and creatinine(Scr).The expressions of TGF-β1,Smad2,Smad3,FN,CTGF and a-SMA m RNA were detected by real-time PCR.Immunohistochemical method was used to detect the expressions of TGF-β1,Smad2/3,FN,α-SMA,Collagen I and Collagen IV related fibrosis.The expressions of TGF-β1,Smad2/3 and p-Smad2/3 protein were measured by western blot.HE,PAS,Sirius Red staining were used to observe the morphological changes and the depositions of glycogen and collagen of renal tissues.Results:Compared with NC group,the blood glucose of SIT group and DM group were significantly increased(P < 0.001).Compared with DM group,the blood glucose of SIT group did not decrease(P > 0.05).At the end of the experiment,urinary microalbumin(2.46 ± 0.97)in SIT group was significantly lower than that(11.96 ± 3.36)in DM group(P < 0.001);BUN(26.08 ± 4.65)and Scr(13.40 ± 2.47)in DM group compared with BUN(10.40 ± 2.47)and Scr(238.51 ± 53.03)in SIT group were greatly lower,respectively(P < 0.01);The renal index(21.43 ± 2.16)in the DM group was higher than that(15.14 ± 4.14)in the SIT group(P < 0.05);Compared with NC group,the expressions of TGF-β1,Smad2,Smad3,FN,CTGF and α-SMA m RNA in DM group were evidently higher than those in DM group(P < 0.05),and the m RNA expressions of above stated factors in SIT group were obviously lower than them in DM group(P < 0.05).Compared with NC group,the contents of FN,Smad2/3,p-Smad2/3,TGF-β1 and α-SMA in DM group were significantly higher than those in NC group(P < 0.05).The protein levels of FN,Smad2/3,p-Smad2/3,TGF-β1,α-SMA,Collagen I and Collagen IV in renal tissues of SIT group were significantly lower than those in DM group(P < 0.05).Conclusions:1.SIT did not decrease blood glucose levels of streptozotocin-induced type 1 diabetes mellitus mice.2.SIT delayed the damages of renal tissue structure and function in T1 DM mice induced by streptozotocin.3.SIT prevented the development of renal injuries in T1 DM mice by inhibiting TGF-β1 / Smad2/3 signaling pathway.