The Effect Of DPP-IV Inhibitor Sitagliptin On The P38MAPK Signaling Pathways In Diabetic Nephropathy Rats

Objective:To investigate the protection of Sitagliptin on apoptosis of diabetic nephropathy podocyte and its effect on P38 MAPK signaling pathway.Methords:Clean level 40 male Wistar rats, according to the random allocation methods will only40 rats were divided into normal control group(NC group), model of diabetic nephropathy(DN), DN model + west Glenn dean 5 mg treatment group(ST1 group), DN model + west Glenn dean 10 mg treatment group(group ST2), average in each group was 10. DN, ST1,30 rats in ST2 group adopts single intraperitoneal injection of chain urea rhzomorph type 2DN model is set up, after the success of the building, ST1 group, the ST2 group were given different doses of west Glenn dean suspension liquid lavage treatment. Respectively at 4, 8,12, 16 w at the end of the 24 h urine protein quantitative determination; At the end of 16 w,put to death in the rat, determination of Glu, Scr, BUN, record the kidney weight and rat body weight, calculate the KW/BW; Take the left kidney tissue of rats were HE, PAS,MASSON staining, immunohistochemical, real-time fluorescent quantitative PCR method for determining P38 MAPK, Caspase 3, Caspase- 8 and podocin protein expression.Results:1. At the end of 16 th week, Glu, Scr and BUN of the rats in DN group, ST 1 group and ST 2 group showed an increase compared with that of NC group; group ST 2 rats compared with ST1 group, Glu, Scr, BUN decreased, the difference was statisticallysignificant(P < 0.05).2. 24 h urine protein quantitation of DN group showed an increased compared with NC group; compared with DN group, 24 h urine protein quantitation of ST 1 and ST 2 groups declined obviously, and the differences of ST 1and ST 2 groups showed statistical significance(P<0.05).3. Kidney weight/body weight(KW/BW) of DN group showed an increased compared with NC 、ST 1 and ST 2,ST2 group than in ST1 group KW/BW decreased, the difference was statistically significant(P < 0.05).4. The pathologic results: renal biopsy after HE, PAS, MASSON staining the visible pathological changes as follows: NC group in addition to the normal glomerulus and renal tubule form visible, no obvious abnormal pathological form; Build module observation can be found that part of glomerular hypertrophy, glomerular basement membrane thickening,see within the interstitial infiltration of inflammatory cells. West Glenn in drug treatment after intervention, the abnormal symptoms improved, and large dose of drug treatment group improved obviously.5. Immunohistochemistry and PCR results showed that except NC group, DN group,ST1 and ST2 group podocyte P38 MAPK signaling pathway, the expression of Caspase-3and Caspase-8 expression increased significantly, the podocyte marker protein on the surface of podocin protein expression was decreased. Compared with DN group, the group ST1, ST2 group of P38 MAPK and Caspase-3 and Caspase-8 expression decreased and increased expression of podocin protein, the difference is statistically significant(P < 0.05),10 mg Sitagliptin dose treatment group, the above changes obviously.Conclusions:1.Sitagliptin can improve the structure and function of DN damage, resulting in effective renal protection.2.Sitagliptin can inhibit p38 MAPK signaling pathway expression in kidney, reduce the apoptosis of podocytes DN.