Renoprotective effect of rosuvastatin in DOCA-salt hypertensive rats.

摘要

BACKGROUND: Pleiotropic effects of statins represent potential mechanisms for the treatment of end organ damage in hypertension. This study has investigated the effects of rosuvastatin (10 mg/kg/day) on renal function impairment, glomerulosclerosis and tubulointerstitial fibrosis in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rat. METHODS: Rats were implanted with DOCA strips (200 mg/kg) on 1 week after unilateral nephrectomy. Rats received a controlled diet with or without rosuvastatin. Three weeks after DOCA implantation, systolic blood pressure (SBP) was measured by tail-cuff method. The glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome stain. The tumour necrosis factor (TNF-alpha), interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), monocyte chemoattractant protein1 (MCP1), intercellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) were determined by real-time polymerase chain reaction. The expression of ED-1, transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) was determined in the kidney by immunoblotting and immunohistochemistry. RESULTS: In DSH rats, SBP was increased, which was not affected by rosuvastatin treatment. Creatinine clearance was decreased while urinary albumin excretion ratio was increased in DSH rats compared with controls, which were attenuated by rosuvastatin treatment. Glomerulosclerosis and tubulointerstitial fibrosis in DSH rats were attenuated by rosuvastatin treatment. The messenger RNA expression of TNF-alpha, IL-1beta, IFN-gamma, MCP1, ICAM-1 and ET-1 was increased in DSH, which was attenuated by rosuvastatin treatment. The expression of ED-1, TGF-beta and CTGF was increased in the kidney of DSH, which was counteracted by rosuvastatin treatment. CONCLUSION: Rosuvastatin is effective in preventing progression of renal injury in DSH, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects.