中文摘要：

目的研究醛固酮（ALD）对肾小球足细胞的损伤作用并探讨醛固酮拮抗剂依普利酮（EPL）、氨氯地平（CCB）和替米沙坦（ARB）对ALD所致损伤的影响及机制。方法30只SD大鼠被随机分为对照组（CTL组）、ALD输注组以及ALD输注并用EPL、CCB或ARB治疗组。以1．5μg／h输注ALD造模，用EPL（100mg·kg-1·d-1）、CCB（10mg·kg-1·d-1）和ARB（3mg·kg-1·d-1）分别灌胃治疗。检测28d内血压及尿白蛋白排泄率（UAER）。于28d处死动物，检测血浆ALD、AngⅡ、血钾、钠、Scr；观察。肾脏光镜和电镜病理改变；TUNEL法检测细胞凋亡；免疫组化和RT—PCR法检测nephrin表达。结果（1）与CTL组相比，ALD组大鼠7d时血压开始升高，28d达高峰（P〈0．01）；EPL组血压和15AER均显著低于同时间点ALD组（P〈0．01）；CCB组UAER显著高于同时间点EPL组，但与ALD组差异无统计学意义。（2）ARB组血浆AngII水平显著高于ALD组、CCB组和EPL组（P〈0．01）。（3）ALD组肾小球出现系膜细胞增殖、系膜外基质增多、足突融合和微绒毛化等病理改变。EPL组肾小球损伤评分和凋亡率显著低于ALD组、CCB组和ARB组（分别P〈0．05，P〈0．01）。（4）ALD组nephrinmRNA和蛋白表达均高于CTL组，EPL组nephrin蛋白和mRNA表达低于ALD组（P〈0．01）。结论ALD输注可诱导肾小球足细胞损伤。CCB和ARB能显著降低血压，但不能减轻ALD所致损伤。EPL可通过非血流动力学作用部分阻断ALD的损伤效应。

英文摘要：

Objective To investigate whether aldosterone infusion induces glomerular or podocyte injury in rats and to evaluate the effects of eplerenoen （EPL）, amlodipine （CCB） and telmisartan （ARB） on aldosteroneinduced injury. Methods Thirty male Sprague-Dawley rats were divided into 5 groups： control, subcutaneous infusion of aldosterone （1.5μg/h, ALD group） and aldosterone infusion plus eplerenone （100 mg·kg-1·d-1, EPL group）, amlodipine（10 mg·kg-1·d-1, CCB group）, telmisartan （3 mg·kg-1·d-1, ARB group）, respectively. Systolic blood pressure（SBP） and urinary albumin excretion ratio（UAER） were measured at day 0, 7, 14, 21, 28. Blood samples were harvested to detect plasma angiotensin Ⅱ, plasma aldosterone, serum sodium, serum potassium and serum creatinine at day 28. Glomerular damge was quantified by morphological glomerular injury score （GIS）. Immunohistoehemistry and RT-PCR were performed to evaluate podoeyte lesion, and apoptosis ratio of podocyte （ARP） in a glomerular cross section was analyzed by TUNEL. Results ALD infusion progressively increased SBP and UAER compared with CTL （P〈0.01）. SBP was significantly reduced in EPL, CCB or ARB-treated animals, meanwhile, UAER was decreased in EPL and ARB group, but not in CCB group. The ALD-infused rats exibited hypernatremia and hypopotassaemia, which were blocked by EPL adminstration but not by CCB or ARB treatment. ARB group had a significant increase in plasma angiotensin Ⅱ compared with ALD, CCB and EPL groups（P〈0.01 ）. The ALD-infused animals developed hyperaldosteronemia compared with CTL, but with no difference of plasma aldosterone among ALD, EPL, CCB and ARB-treated rats. Treatment with EPL prevented an increase of GIS and ARP compared with CCB and ARB（P 〈0.05, P〈0.01）. Protein and mRNA expression of nephrin was up-regulated in ALD group （P〈 0.01 ）, but was significantly prevented by EPL treatment（P〈O.O1 ）, whereas CCB and ARB therapy had no such effect. Conclusion ALD infusi