| Autor: |
Vieira Jr., J. M., Rodrigues, L.T., Mantovani, E., Dellê, H., Mattar, A. L., Malheiros, D. M. A. C., Noronha, I. L., Fujihara, C. K., Zatz, R. |
| Předmět: |
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| Zdroj: |
Nephron Physiology; 2005, Vol. 101 Issue 4, pp82-p91, 10p, 1 Black and White Photograph, 1 Chart, 4 Graphs |
| Abstrakt: |
Background: Several salutary biological effects of statins have been described. We sought to investigate more closely the anti-inflammatory and antiproliferative effects of simvastatin (SIMV) in a model of hypertension and progressive renal disease, as well as its effects on the cyclin-cdk inhibitors p21 and p27. Methods: Munich-Wistar rats received the nitric oxide (NO) synthase inhibitor L-NAME (25 mg/kg/day p.o.) for 20 days accompanied by a high-salt diet (HS, 3% Na) and then were kept on HS for 60 days. Animals were then divided into two groups: vehicle (VH) or SIMV 2 mg/kg/day p.o. Albuminuria and tail-cuff pressure were determined at 30 and 60 days. RT-PCR was done to assess renal expression of TGF-β1, collagen I and III, fibronectin, p27, p21 and monocyte chemoattractant protein-1 (MCP-1). Renal protein expression was assessed by Western blot (proliferating cell nuclear antigen (PCNA)) and immunostaining (macrophage, lymphocyte, PCNA). Results: SIMV did not prevent the development of severe hypertension or albuminuria. SIMV-treated animals had less severe renal interstitial inflammation and cell proliferation. MCP-1 expression was significantly diminished in the SIMV-treated animals (55.4 ± 7.3 vs. 84.4 ± 8.2 OD, p = 0.02). mRNA renal expression for p27 and TGF-β did not change between groups, but p21 mRNA renal expression, highly induced in this model, significantly decreased with SIMV treatment (31.6 ± 6.6 vs. 50.2 ± 5.8 OD, p < 0.05). The interstitial fibrosis score significantly decreased with SIMV (2.46 ± 0.40 vs. 4.07 ± 0.38%, p < 0.01), which was confirmed by a decrease in renal collagen I and fibronectin expression. Serum cholesterol level did not change with SIMV. Conclusion: SIMV attenuated interstitial fibrosis associated with this model of hypertensive renal disease. The mechanism involved MCP-1 downregulation. SIMV treatment was also associated with a p21 downregulation in the kidney, which might be involved in the protection of renal scarring. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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