Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757, Korea.
Nephrol Dial Transplant. 2010 Apr;25(4):1051-9. doi: 10.1093/ndt/gfp604. Epub 2009 Nov 30.
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.
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.
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.
Rosuvastatin is effective in preventing progression of renal injury in DSH, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects.
他汀类药物的多效性代表了治疗高血压终末器官损伤的潜在机制。本研究探讨了瑞舒伐他汀（10mg/kg/天）对醛固酮盐性高血压（DSH）大鼠肾功能损害、肾小球硬化和肾小管间质纤维化的影响。
单侧肾切除后 1 周，大鼠植入去氧皮质酮（DOCA）带（200mg/kg）。大鼠给予含或不含瑞舒伐他汀的对照饮食。DOCA 植入 3 周后，用尾套法测量收缩压（SBP）。Masson 三色染色法测定肾小球硬化和肾小管间质纤维化。实时聚合酶链反应测定肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、单核细胞趋化蛋白 1（MCP1）、细胞间黏附分子-1（ICAM-1）和内皮素-1（ET-1）。免疫印迹和免疫组化法测定肾脏中 ED-1、转化生长因子-β1（TGF-β1）和结缔组织生长因子（CTGF）的表达。
DSH 大鼠 SBP 升高，瑞舒伐他汀治疗未影响 SBP。与对照组相比，DSH 大鼠肌酐清除率降低，尿白蛋白排泄率增加，瑞舒伐他汀治疗可减轻这些变化。DSH 大鼠肾小球硬化和肾小管间质纤维化减轻，瑞舒伐他汀治疗可降低 TNF-α、IL-1β、IFN-γ、MCP1、ICAM-1 和 ET-1 的 mRNA 表达。DSH 大鼠肾脏 ED-1、TGF-β 和 CTGF 表达增加，瑞舒伐他汀治疗可拮抗这些变化。
瑞舒伐他汀可有效预防 DSH 大鼠肾脏损伤进展，其机制与抗炎和抗纤维化作用有关。
