Simvastatin protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression

Abstract

Objective: To observe the effects of simvastatin on urinary excretion of matrix metalloproteinase-9 (MMP- 9), renal expression of MMP-9, and investigate its possible renoprotective mechanisms in streptozotocin (STZ)-induced diabetic rats.

Method: Twenty-four Wistar rats were divided into 3 groups: control healthy rats (group C, no.=8), untreated diabetic rats (group D, no.=8), and diabetic rats treated with simvastatin (20 mg/kg/d) (group S, no.=8). Peripheral blood glucose was tested weekly, glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C) levels, and urinary albumin (ALB) excretion rate as well as the urinary excretion rates of retinol-binding protein (RBP) and MMP-9 were tested at 8th week. The renal tissues of diabetic rats were obtained for evaluating kidney/ body weight ratio, observing renal pathological changes by electron microscope and examining the expression of renal MMP-9 mRNA by RT-PCR.

Results: There was no statistical difference on the change of peripheral blood TC and LDL-C between group C and group D. Peripheral blood glucose, HbA1c levels kidney/body weight ratio urinary excretion rates of ALB, RBP, and MMP-9 concurrently with the expression of renal MMP-9 mRNA were significantly higher in groups D and S compared with group C (p<0.01). Treatment with simvastatin significantly lowered peripheral blood TC, LDL-C, kidney/body weight ratio, urinary excretion rates of ALB, RBP, and MMP-9 as well as the expression of renal MMP-9 mRNA (p<0.01); however, there was no evident effect on the change of blood glucose and HbA1c levels between group D and group S. In addition, urinary excretion rate of MMP-9 showed positive correlations with the urinary ALB excretion and urinary RBP excretion. Pathological lesions of the glomeruli and epithelial cells foot processes (FP) was lightened by simvastatin.

Conclusion: Simvastatin may has a potential therapeutic target in diabetic nephropathy, which may be partly attributed to down-regulating over-expression of MMP-9 in renal tissue.