SIMVASTATIN ATTENUATES RENAL FAILURE IN MICE WITH A 5/6 SUBTOTAL NEPHRECTOMY
Objective: The objective of this study to investigate the effect of simvastatin on kidney fibrosis in mice with a 5/6 subtotal nephrectomy.
Methods: Thirty adults (3 mo old) male Swiss mice were submitted to a 5/6 subtotal nephrectomy and studied after 14 d. Animals were divided into five groups: 5/6 subtotal nephrectomy (SN, n=6), sham operation (SH, n=6), simvastatin 5.2 mg/kg body weight (SIM-1, n=6), simvastatin 10.4 mg/kg body weight (SIM-2, n=6), and simvastatin 20.8 mg/kg body weight (SIM-3, n=6) groups. At sacrifice, kidneys were harvested for morphology (glomerulosclerosis (GS), tubular injury and interstitial fibrosis), immunostaining (Î±-smooth muscle actin (Î±-SMA)) and platelet-derived growth factor receptor beta (PDGF-RÎ²) and reverse transcriptase-polymerase chain reaction (RT-PCR) (MCP-1, ICAM-1, nephrin, and podocin) analysis.
Results: Glomerulosclerosis, tubular injury and interstitial fibrosis in the simvastatin group was significantly lower than SN group (p<0.05). Simvastatin significantly reduced Î±-SMA expression (3.61Â±1.06 vs 7.91Â±1.26, p<0.05, SIM-1 vs SN; 2.86Â±0.61 vs 7.91Â±1.26, p<0.05, SIM-2 vs SN; 1.71Â±0.50 vs 7.91Â±1.26, p<0.05, SIM-3 vs SN), MCP-1 was markedly expressed in the 5/6 subtotal nephrectomy kidneys and was reduced with simvastatin (1.4Â±0.64 vs 0.57Â±0.23, p<0.05, SN vs SIM-1; 1.4Â±0.64 vs 0.6Â±0.26, p<0.05, SN vs SIM-2; 1.4Â±0.64 vs 0.52Â±0.21, SN vs SIM-3, p<0.05). Simvastatin did not increase nephrin expression, but it increased podocin expression significantly in the SIM-3 group.
Conclusion: Simvastatin significantly attenuated GS, tubular injury and interstitial fibrosis through the downregulation of myofibroblast expansion and inflammatory mediators in mice with a 5/6 subtotal nephrectomy.
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