| Objective:To investigate the effects of different doses of metforminon expression of renal tissue podocalyxin (PCX) in Type 2 diabetes model rats and explore its possible protective effect and mechanism to kidney podocytes.Methods:Type 2 diabetes model of rats were induced by a high-fat diet combined with low dose of streptozotocin.,Sprague-Dawley rats were randomly divided into five groups:control healthy rats (group NC); untreated type 2 diabetic rats (group DM); glibenclamide intervention group (group GLY,5 mg-kg-1·d-1); type 2 diabetic rats treated with different doses of metformin (150,300,500 mg·kg-1·d-1, group M1, M2, M3, respectively). In the end of study, the level of urinary albumin,urinary PCX and urine creatinine were measured. Then the value of urinary albumin/creatinine(UACR) and urinary PCX/creatinine(UPCR) were calculated. The level of blood glucose (BG), glycated hemoglobin (HbAlc), blood urea nitrogen(BUN) triacylglycerol(TG) and low density lipoprotein(LDL-C) were tested. Immunohistochemical method was used to observe the renal tissue PCX protein expression. Real-Time PCR was applicated to detect PCX mRNA expression. Renal tissue pathological changes were observed by electron microscope.Results(1) Compared with group NC, the level of BG, HbAlc, BUN,TG,LDL-C in group DM rats increased significantly (P< 0.05).After metformin treatment for 8 weeks, compared with group DM, the level of those significantly reduced (P< 0.05).Compared with group GLY, the level of BUN,TG,LDL-C in group M2,M3 significantly reduced(P< 0.05).(2)At the 8th week, the level of UACR and UPCR in group DM rats increased compared with group NC(P< 0.05). Metformin treatment obviously decreased the level ofUACR and UPCR as compared to group DM (p< 0.05). The higher dose of metformin (300,500mg/kg) more noticeably caused decrease in UACR and UPCR as compared to group GLY (P< 0.05).(3) Effect of Metformin on the Renal Histopathological Changes:Histopathological examination of kidney tissue obtained from NC rats showed normal GBM without foot process fusion. However, both the foot process fusion (nearly 80%) and GBM and GBMT were found increased significantly in T2DM rats (P< 0.05). Both FRFP and GBMT were alleviated by MET treatment compared to those of group DM (P< 0.05). Compared to GLY treatment, GBMT decreased much more in higher doses of metformin (groupsM2, M3) (P< 0.05) and FRFP was restored to 15% in M3 group (P< 0.05).(4) Effect of Metformin on the Renal Tissue PCX Protein and mRNA Expressions in Rats. To investigate the role of metformin regulating the expression of PCX in renal tissue. PCX protein expression decreased significantly in five diabetic groups which was accompanied with a significant decrease in PCX mRNA expression, especially in group DM (P< 0.05) when compared to the group NC. Treatment rats with different doses of metformin significantly restored the decreased protein and mRNA expression of PCX, which was more prominent in higher dose of metformin group (300,500mg/kg) than GLY group (P< 0.05).Conclusion(1) Metformin can play a role in protecting the glomerular podocytes by adjusting the renal tissue expression of PCX in Type 2 diabetes mellitus model rats.(2) The effect of metformin in protecting the glomerular podocytes by adjusting the renal tissue expression of PCX in Type 2 diabetes mellitus model rats was beyond its hypoglycemic effects and with a does-dependent manner. |
PDF Full Text Request