Division of Urology, Department of Surgery, University of São Paulo School of Medicine, São Paulo, Brazil.
Urology. 2012 Aug;80(2):485.e15-20. doi: 10.1016/j.urology.2012.02.021. Epub 2012 Apr 13.
To assess the effects of atorvastatin (ATORV) on renal function after bilateral ureteral obstruction (BUO), measuring inulin clearance and its effect on renal hemodynamic, filtration, and inflammatory response, as well as the expression of Aquaporin-2 (AQP2) in response to BUO and after the release of BUO.
Adult Munich-Wistar male rats were subjected to BUO for 24 hours and monitored during the following 48 hours. Rats were divided into 5 groups: sham operated (n = 6); sham + ATORV (n = 6); BUO (n = 6); BUO + ATORV (10 mg/kg in drinking water started 2 days before BUO [n = 5]; and BUO + ATORV (10 mg/kg in drinking water started on the day of the release of BUO [n = 5]). We measured blood pressure (BP, mm Hg); inulin clearance (glomerular filtration rate [GFR]; mL/min/100 g); and renal blood flow (RBF, mL/min, by transient-time flowmeter). Inflammatory response was evaluated by histologic analysis of the interstitial area. AQP2 expression was evaluated by electrophoresis and immunoblotting.
Renal function was preserved by ATORV treatment, even if initiated on the day of obstruction release, as expressed by GFR, measured by inulin clearance. Relative interstitial area was decreased in both BUO + ATORV groups. Urine osmolality was improved in the ATORV-treated groups. AQP2 protein expression decreased in BUO animals and was reverted by ATORV treatment.
ATORV administration significantly prevented and restored impairment in GFR and renal vascular resistance. Furthermore, ATORV also improved urinary concentration by reversing the BUO-induced downregulation of AQP2. These findings have significant clinical implication in treating obstructive nephropathy.
评估阿托伐他汀（ATORV）对双侧输尿管梗阻（BUO）后肾功能的影响，通过测量菊粉清除率及其对肾血流动力学、滤过和炎症反应的影响，以及水通道蛋白-2（AQP2）的表达，来评估 BUO 及 BUO 解除后对其的影响。
成年雄性 Munich-Wistar 大鼠进行 24 小时 BUO 处理，并在接下来的 48 小时进行监测。大鼠分为 5 组：假手术组（n = 6）；假手术+ATORV 组（n = 6）；BUO 组（n = 6）；BUO+ATORV 组（10 mg/kg 阿托伐他汀于 BUO 前 2 天开始饮水[ n = 5]）；以及 BUO+ATORV 组（10 mg/kg 阿托伐他汀于 BUO 解除当天开始饮水[ n = 5]）。我们测量了血压（BP，mmHg）；菊粉清除率（肾小球滤过率[GFR]；mL/min/100 g）；和肾血流量（RBF，mL/min，通过瞬时流量计）。通过间质面积的组织学分析评估炎症反应。通过电泳和免疫印迹评估 AQP2 表达。
即使在梗阻解除当天开始治疗，阿托伐他汀治疗也能保护肾功能，这表现为 GFR 通过菊粉清除率测量。在 BUO+ATORV 两组中，相对间质面积减少。在阿托伐他汀治疗组中，尿渗透压得到改善。AQP2 蛋白表达在 BUO 动物中减少，并通过阿托伐他汀治疗得到逆转。
阿托伐他汀的给药显著预防和恢复了 GFR 和肾血管阻力的损害。此外，阿托伐他汀还通过逆转 BUO 诱导的 AQP2 下调来改善尿浓缩。这些发现对治疗梗阻性肾病具有重要的临床意义。
