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


METHODS
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.


CONCLUSIONS
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.
Yao
X-M
XM
Department of Endocrinology, Anhui Provincal Hospital, Anhui Medical University, Hefei, China.
Ye
S-D
SD
Zai
Z
Z
Chen
Y
Y
Li
X-C
XC
Yang
G-W
GW
Wang
Y-X
YX
Chen
K
K
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D050533:Glomerular Basement Membrane / Q000201:enzymology / Q000473:pathology; D006442:Glycated Hemoglobin / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008854:Microscopy, Electron; D009929:Organ Size / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use*
D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019821:Simvastatin