Effect Of Sitagliptin On Expressions Of JNK In Diabetic Nephropathy Rats Kidney

Objectives:To investigate the effect of sitagliptin on the expressions of Nephrin and c-Jun Nterminal kinase(JNK) in diabetic nephropathy rats kidney.Methods:Forty male Wistar rats were randomly divided into normal control group(NC group, n=10),diabetic mellitus group(DM group, n=10),sitagliptin treatment group1(ST1group,5mg,n=10)and sitagliptin treatment group2(ST2 group,10 mg,n=10).NC group had access to standard chow and water ad libitum. Model group(DM group,ST1 group and ST2 group)had access to high sucrose-fat diet. After 4weeks,Model group allocated to be made diabetic received peritoneally injections of streptozotocin(STZ,40mg/kg body weight).NC group received injections of distilled wate.We included only rats with blood glucose concentrations which was not less than16.7 mmol/L in the diabetes group.After the success of the model, Sita1 group(Sitagliptin with the dose of 5mg/kg body weight daily) and Sita2 group(Sitagliptin with the dose of 10mg/kg body weight daily) used intragastric administration by 8weeks.DM group and NC group rats were received the equal volume of physiological saline. NC group rats were fed with the standard chow, while the remaining three groups were fed with the high fat diet. At the end of the 16 weeks,urine samples for 24 h were collected to examine urinary,analysis BUN and SCr.The morphological changes of renal tissues were observed after HE、PAS、Masson、PASM staining. Immunohistochemistry and real-time fluorescence quantification PCR method to detect the expression of GLP-1、DPP-IV、 Nephrin and JNK.Results:1.Four groups of rats were observed under section: NC group rat glomerular structure not seen obvious abnormity; DM group rat glomerular volume increased obviously and hyperemia, glomerular balloon lumen narrowed adhesion, obvious thickening of glomerular basement membrane, mesangial matrix proliferation. ST1 and ST2 groups have different degrees of ease, ease ST2 group more clearly.2.At the end of 16 th week, compared with NC group, DM group rats 24 h urine trace albumin quantitative, BUN, Scr rose obviously(p<0.05); Compared with DM group, ST1 with ST2 group of 24 h urine trace albumin quantitative, blood BUN, Scr declined obviously, the difference was statistically significant(p<0.05); Group compared with ST1 group,ST2 group of 24 h urine glucose,BUN, Scr changed more obviously, the difference was statistically significant(p<0.05).3.Immunohistochemical result:compared with NC group, DM group of GLP-1,nephrin declined obviously, DPP-IV, c-jun rose obviously(p<0.05); compared with DM group, ST1 and ST2 Group with GLP-1, nephrin rose obviously, DPP-IV, c-jun declined obviously(p<0.05);compared with ST1, ST2 group changed more obvious,the difference was statistically significant(p<0.05). Correlation analysis: glomerular JNK expression and nephrin in DM group(r=0.769, p<0.05) was positively correlated.4.Real-time fluorescence quantification PCR display:compared with NC group,DM group of GLP-1, nephrin m RNA expression is reduced, the DPP-IV, c-jun m RNA expression increased(p<0.05); compared with DM group, ST1 and ST2 group GLP-1,nephrin m RNA expressionrose obviously, DPP-IV, c-jun m RNA expression of lower(p<0.05).compared with ST1 group,ST2 group changed more obvious, the difference was statistically significant(p<0.05).Conclusions:Sitagliptin has some protective effect on diabetic rats, probably by inhibiting JNK signal pathway of kidney of diabetic nephropathy rats activity and up-regulating the expression of Nephrin in the renal tissue.