Intervention effect of sitagliptin on diabetic nephropathy in type 1 diabetic mice
10.13699/j.cnki.1001-6821.2017.22.016
- VernacularTitle:西格列汀对1型糖尿病小鼠肾病的干预作用
- Author:
Zhen ZHANG
1
;
Yan-Jie TENG
;
Yi-Fei LIAN
;
Bin ZHANG
;
Shu-Hong ZHENG
;
Lu-Xin LI
;
Yan-Hui CHU
;
Xu LIAN
Author Information
1. 牡丹江医学院第一临床医学院
- Keywords:
sitagliptin;
type 1 diabetes mellitus;
nephropathy disease;
transforming growth factor-β1
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(22):2269-2272
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the intervention effect and mechanism of sitagliptin on renal injury in type 1 diabetic (T1DM) mice.Methods The modeling 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 groups:model group and experimental group.Experimental group was treated with sitagliptin (15 mg · kg-1 · d-1) via intragastric administration for 4 weeks while the mice in model group and normal group treated with equal volume of ultrapure water.The 24 h microalbuminuria(ALB) was determined after administration.At the end of the experiment,urea nitrogen (BUN) and creatinine (SCr) in serum was detected.The protein expression levels of transforming growth factor-β1 (TGF-β1),Smad2,Smad3 were measured by Western blot.Results After administration sitagliptin for 4 weeks,the contents of ALB in model group and experimental group were (11.96 ± 3.36) (2.46 ±0.97) mg/24 h with significantly(P ＜0.001).The index of kidney weight/body weight(KW/BW) in normal group,model group and experimental group were 15.20 ±2.24,21.43 ±2.16,15.14 ±4.14;compared with normal group,the difference was significantly increased (P ＜ 0.05);compared with model group,the difference was significantly increased (P ＜0.05).The SCr in model group and experimental group were (352.58 ±47.09),(238.51 ± 53.03) μmol · L-1;the BUN in the two groups were(26.08 ±4.65),(10.40 ±2.47)mmol · L-1;compared with model group,the difference was significantly increased (P ＜0.01,P ＜0.001).The expression levels of TGF-β1,Smad2/3 and p-Smad2/3 in normal group,model group and experimental group were 0.19 ±0.02,0.12 ±0.02,0.07 ±0.01;0.23 ±0.02,0.27 ±0.04,0.13 ±0.01;0.18 ±0.01,0.14 ±0.01,0.11 ±0.00,compared with normal group,the difference was significantly increased (P＜0.05,P＜0.01);compared with model group,the difference was significantly increased (P ＜0.05,P ＜0.01).Conclusion Experimental delaying the progression of T1DM nephropathy without not decreasing blood glucose can effect partly through inhibiting TGF-β1/Smad2/3 pathway.
