Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress
Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress
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DOI：
10.1159/000355736
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Liu, Yan
中科院分区：
文献类型：
--
作者：
Chen, Hui;Sun, Feng;Liu, Yan
背景/目的：血清醛固酮持续升高导致肾纤维化。炎症也在肾脏疾病的发病机制中起作用。我们使用大鼠间质性肾纤维化模型来检验依普利酮介导的醛固酮阻断剂由于其抗炎和抗增殖作用而防止肾纤维化的假设。研究方法：依普利酮（选择性醛固酮阻滞剂）或车辆（对照），给予雄性Wistar大鼠（50毫克/公斤，每天两次）7天前单侧输尿管梗阻（UUO）和手术后额外的28天。术后7、14和28天，测定两组的体重、血压、肾组织形态学、巨噬细胞免疫染色、单核细胞趋化蛋白-1、增殖细胞核抗原、α-平滑肌肌动蛋白以及肾功能和氧化应激的血清和尿液标志物。结果：依普洛酮对体重和血压无影响。然而，依普利酮抑制肾纤维化、炎症（巨噬细胞和单核细胞浸润）、间质细胞增殖和间质细胞活化（α-SMA表达）的发展。Epleronone还降低氧化应激。结论：依普利酮的抗肝纤维化作用与其对血压的影响无关。依普利酮抑制肾脏炎症、间质细胞增殖、间质细胞表型改变，并降低氧化应激。版权所有（C）2013 S. Karger AG，巴塞尔
Background/Aims: Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects. Methods: Eplerenone (a selective aldosterone blocker) or vehicle (control), was given to male Wistar rats (50 mg/kg, twice daily) for 7 days before unilateral ureteral obstruction (UUO) and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immuno-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, alpha-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery. Results: Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration), interstitial cell proliferation, and activation of interstitial cells (alpha-SMA expression). Epleronone also reduced oxidative stress. Conclusion: The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress. Copyright (C) 2013 S. Karger AG, Basel