Mineralocorticoid Receptor Blocker Protects against Podocyte-Dependent Glomerulosclerosis.

Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-01-31 DOI:10.1159/000334961

Nobuaki Takagi, Takakuni Tanizawa, Valentina Kon, Agnes B Fogo, Iekuni Ichikawa, Ji Ma

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引用次数: 9

Abstract

Background: We previously showed that angiotensin type 1 receptor (AT1) blocker (ARB) attenuates glomerular injury in Nphs1-hCD25 (NEP25) transgenic mice, a model of selective podocyte injury. However, subsequent studies in NEP25 mice with podocyte-specific deficiency of AT1 revealed that the protective effects of ARB are not through the podocyte AT1, thereby raising the possibility that the protective effects of ARB involve mineralocorticoids. Methods: NEP25 mice were treated with the mineralocorticoid receptor blocker (MRB) spironolactone (25 mg/kg/day, n = 10), the ARB losartan (250 mg/kg/day, n = 11), both (ARB+MRB, n = 8) or vehicle (Vehicle, n = 9) from day –7 to day 9 of induction of podocyte injury. Results: Although MRB did not reduce systolic blood pressure or proteinuria, addition of MRB to ARB significantly attenuated glomerulosclerosis (glomerulosclerosis index: ARB+MRB 1.67 ± 0.19 vs. MRB 2.01 ± 0.29, ARB 2.35 ± 0.19, and Vehicle 2.25 ± 0.26, p < 0.05) and preserved the number of WT1-positive podocytes (ARB+MRB 152.5 ± 9.7 vs. MRB 117.2 ± 9.0 or ARB 113.6 ± 7.4, and ARB+MRB vs. Vehicle 97.5 ± 4.0 per glomerulus; p < 0.05). Conclusion: These data suggest that, while MRB does not attenuate proteinuria caused by podocyte-specific injury, it provides protective effects against glomerulosclerosis that is independent of systemic blood pressure.

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矿皮质激素受体阻滞剂可预防足细胞依赖性肾小球硬化。

背景:我们之前发现血管紧张素1型受体(AT1)阻滞剂(ARB)可以减轻Nphs1-hCD25 (NEP25)转基因小鼠(一种选择性足细胞损伤模型)的肾小球损伤。然而，随后对足细胞特异性AT1缺乏的NEP25小鼠的研究表明，ARB的保护作用不是通过足细胞AT1发挥的，从而提出了ARB的保护作用可能涉及矿物皮质激素的可能性。方法:从诱导足细胞损伤的第7天至第9天，分别给予矿皮质激素受体阻阻剂(MRB)内酯(25 mg/kg/day, n = 10)、ARB氯沙坦(250 mg/kg/day, n = 11)、ARB+MRB (n = 8)或载药(vehicle, n = 9)。结果:虽然MRB没有降低收缩压或蛋白尿，但在ARB中加入MRB可显著减轻肾小球硬化(肾小球硬化指数:ARB+MRB 1.67±0.19 vs MRB 2.01±0.29,ARB 2.35±0.19，和Vehicle 2.25±0.26,p < 0.05)，并保留wt1阳性足细胞数量(ARB+MRB 152.5±9.7 vs MRB 117.2±9.0或ARB 113.6±7.4,ARB+MRB vs Vehicle 97.5±4.0);P < 0.05)。结论:这些数据表明，虽然MRB不能减轻足细胞特异性损伤引起的蛋白尿，但它对独立于全身血压的肾小球硬化具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nephron Extra

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： An open-access subjournal to Nephron. ''Nephron EXTRA'' publishes additional high-quality articles that cannot be published in the main journal ''Nephron'' due to space limitations.