The Protective Effects of Valsartan on Kidney of Diabetic Rats and Its Effects on NHE3Expression
|School||Zunyi Medical College,|
|Keywords||Diabetic nephropathy Valsartan Mixed protamine zinc recombinant humaninsulin Sodium hydrogen exchanger3|
Objective:To investigate the protective effects of valsartan in renal tubule of diabetic rats, and study its possible mechanisms related to sodium hydrogen exchanger3expression, which providing new theory basis for the prevention and treatment of diabetic nephropathy.Methods:The adult male rats were randomly divided into normal control rats (group NC), streptozotocin-induced diabetic rats (group DM), diabetic rats treated with valsartan (30mg/kg/d by gavage, group DV), diabetic rats treated with valsartan and insulin (30mg/kg/d by gavage and2U/d by hypodermic injection, group DVY), diabetic rats treated with insulin (2U/d by hypodermic injection, group DY).6weeks later, blood glucose (BG), renal heavy index, blood urea nitrogen (BUN), serum creatinine (Scr) and24-hour urinary protein (24h-Upro) were measured. The changes of the pathologic feature of the kidney by Hematoxylin-eosin Staining (HE) and Schiff Periodic Acid Shiff Staining (PAS). NHE3protein and mRNA expression in renal tubule were measured by Western blot technique and Real-time quantitative fluorescence PCR (RT-PCR) respectively. Results are expressed as mean±SEM. Statistical comparisons between groups were made by one-way analysis of variance (ANOVA), with pairwise multiple comparisons made by Fisher s protected least-significant differences test. Analyses were performed using the software package SPSS16.0. P-value<0.05were considered significantly.Results:1.The renal heavy index and24-hour urinary protein were higher in group DM than that in group NC (P<0.01). The above-mentioned data were significantly reduced in group DV, DVY and DY, however, were higher than that in group NC (P<0.01).2. Compared with group NC, BUN and Scr were significantly increased in other groups (P <0.01). BUN and Scr concentrations in group DV, DVY and DY were lower than that group DM (P<0.05), but group DVY was obviously reduced (P<0.01). The blood glucose level of group DM, DV, DVY and DY higher than that of group NC (P<0.01), but group DVY and DY much lower than group DM, DV (P<0.01).3.6weeks later, it would be obviously observed under light microscopy in group DM that glomerular volume increased, extracellular matrix (ECM) accumulated and glomerular base membrane massively thickened. The pathological changes in group DV, DVY and DY were less obvious than those in group DM.4. The expression level of NHE3protein in renal tubule, estimated by Western blot technique, was a significant increase in expression of NHE3in group DM compared with that in group NC (P<0.01).5. Compared with group NC, by the Real-time quantitative fluorescence PCR showed that increased3.63folds in group DM, increased2.57folds in group DV, increased3.10folds in DY and only increased1.91folds in group DVY with the expression level of NHE3mRNA in renal tubule.Conclusions:1.The expression of NHE3in renal tubule may increase in diabetic nephropathy, which contributing to the occurance and development of diabetic nephropathy;2. Valsartan has renal protective effect on diabetic rats which may partly through reducing NHE3expression;3. Combination of valsartan and insulin have cooperative protection in diabetic nephropathy.