Impacts of blood glucose fluctuation on renal pathologic changes and IGF-1, MMP-2 expression

Objective To investigate the impacts of blood glucose fluctuation on renal pathologic changes and IGF-1,MMP-2 expression.Methods Forty five male Sprague-Dawley (SD) rats were divided into two groups according to random number table method:experimental group (DM group,n =35) and normal control group(N group,n =10).Streptozotocin (35 mg/kg) was used to induce diabetes.SD rats were fed with high sugar and high fat diet for 4 weeks,and then were divided into fluctuating blood glucose group(F group,n =17) and continuous high blood glucose group (C group,n =17).The rats in F group were given intraperitoneal injection of insulin and glucose at different time points every day.The same volume of physiological saline was given to rats in C and N group.High sugar and high fat diets were maintained in rats in F and C group,while ordinary diet were given to the rats in N group.12 weeks later,24 hours urine protein,blood urea nitrogen,serum creatinine were determined,HE and PAS staining were used to observe the renal morphology,and electron microscopy was applied to observe the ultrastructural change of kidney.Expression of IGF-1 and MMP-2 were determined by immunohistochemistry.Results Rats of F group suffered more serious blood glucose fluctuation with CV value significantly higher than that in rats of C and N group.No significant difference of HbA1c between rats of F and C group,while both higher than rats of N group.Compared with C group,rats in F group showed higher 24 hours urinary protein,kidney hypertrophy index,glomerulosclerosis index,thicker of glomerular basement membrane,and greater elevation of IGF-1 expression,while less MMP-2 expression(all P＜0.05).Conclusions Blood glucose fluctuation may aggravate diabetic kidney damage,the mechanism of which may be related to the upregulation of IGF-1,while downregulation of MMP-2. Key words: Blood glucose variation;  Diabetic nephropathy;  IGF-1 ;  MMP-2