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.
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 diabeticrats. METHOD: Twenty-four Wistar rats were divided into 3 groups: control healthy rats (group C, no.=8), untreated diabeticrats (group D, no.=8), and diabeticrats 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 diabeticrats 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.
Authors: S Lopez; F Peiretti; B Bonardo; P Deprez-Beauclair; H Laouenan; I Juhan-Vague; G Nalbone Journal: J Cardiovasc Pharmacol Date: 2001-06 Impact factor: 3.105
Authors: L Vincent; W Chen; L Hong; F Mirshahi; Z Mishal; T Mirshahi-Khorassani; J P Vannier; J Soria; C Soria Journal: FEBS Lett Date: 2001-04-27 Impact factor: 4.124
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