Effects Of Metformin On AGEs Expression Of Renal Tissue In Type 2 Diabetic Rats

Objective To observe the influences of metformin(MET)on the expression of renal tissue advanced glyclation end-products(AGEs)protein and its receptor m RNA(RAGE m RNA)in Type 2 diabetes(T2DM)model rats,and to discuss the mechanism of the MET in the treatment of DN.Methods 10 SD rats were randomly selected as normal control group(NC group),the remaining rats for type 2 diabetes mellitus model group.The model rats of T2 DM were established by being fed with high fat-diet and intraperitoneal injection of low dose of streptozotocin(STZ).All model rats were randomly divided into metformin group(MET,300 mg.kg-1·d-1),glyburide group(GLY,5mg.kg-1.d-1)and T2 DM model group(T2DM).After 8 weeks observation,blood glucose(BG),glycated hemoglobin(Hb A1c),urinary albumin,urinary albumin/urine creatinine(UACR),urinary AGEs/urine creatinine were detected.Renal tissue pathological changes were observed by electron microscope.The expression of renal tissue AGEs was detected by using immunohistochemistry assay,and the expression of RAGE-m RNA by using Real-time PCR.Results(1)Compared with group NC,the level of BG,Hb A1 c,in group T2 DM ?MET and GLY group rats increased significantly(P < 0.05).After metformin and glyburide treatment for 8 weeks,compared with group DM,the level of those significantly reduced(P <0.05).The level of BG,Hb A1 c was not statistically significant between MET and GLY group(P >0.05);(2)The level of urinary UGCR and UACR in T2 DM increased compared with group NC(P < 0.05).Metformin and glyburide treatment obviously decreased the level of UGCR and UACR as compared to group T2DM(p< 0.05).And in group MET was lower than that in group GLY(P<0.05).(3)The level of urinary renal tissue AGEs and RAGE m RNA increased compared with group NC(P < 0.05).Metformin and glyburide treatment obviously decreased the level of AGEs and RAGE m RNA as compared to group T2DM(p< 0.05).And in group MET was lower than that in group GLY(P<0.05).(4)Pathological results of rat kidney under electron microscope showed that: in the NC group,the structure of podocytes was normal and the thickness of basement membrane was uniform.In group T2 DM,the basement membrane was obviously thickened,the foot process was fused and the structure was indistinct.The level of GBMT compared with group NC(P < 0.05).Metformin and glyburide treatment obviously decreased the level of GBMT as compared to group T2DM(p< 0.05).And in group MET was lower than that in group GLY(P<0.05).Conclusion MET can reduce the accumulation of AGEs in the glomerular,and regulate downwards the over-expression of RAGE-m RNA in T2 DM rats,and this effect is not entirely dependent on the hypoglycemic,which may partly contribute to its reno-protection.