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目的:探讨醛固酮(Ald)灌注对大鼠足细胞损伤的影响及醛固酮特异性拮抗药依普利酮的干预作用。方法:SD大鼠随机分为3组:对照组(A)、醛固酮灌注组(B)、依普利酮治疗组(C),分别皮下埋置渗透性微泵。B、C组均以1.5μg·h~(-1)持续灌注Ald,A组以DMSO代替Ald。C组以依普利酮(100 mg·kg~(-1)·d~(-1))灌胃,A、B组以0.9%氯化钠溶液灌胃。每两周测量尾动脉压,收集24 h尿液检测尿白蛋白排泄率(UAER)。于第28 d处死,PAS染色观察肾小球病理改变,免疫组化染色观察nephrin表达改变。结果:与A组相比,B组平均收缩压和UAER显著上升(P<0.05),nephrin表达增加;C组平均收缩压和UAER较同期B组显著降低(P<0.05),nephrin表达减少。结论:依普利酮可通过改变肾小球足细胞nephrin表达水平,减轻醛固酮诱导的足细胞损伤。
Objective: To investigate the effects of aldosterone (Ald) infusion on podocyte injury in rats and the effect of eplerenone, an aldosterone-specific antagonist. Methods: SD rats were randomly divided into 3 groups: control group (A), aldosterone infusion group (B) and eplerenone treatment group (C). Aldrich was continuously perfused with 1.5μg · h ~ (-1) in group B and C, and Ald was replaced by DMSO in group A. Group C was treated with eplerenone (100 mg · kg -1 · d -1), while group A and B were orally gavaged with 0.9% sodium chloride solution. Tail arterial pressure was measured every two weeks and urinary albumin excretion rate (UAER) was collected 24 h urine. At the 28th day, the rats were sacrificed and the pathological changes of glomeruli were observed by PAS staining. The expression of nephrin was observed by immunohistochemistry. Results: Compared with group A, the average systolic blood pressure and UAER in group B were significantly increased (P <0.05) and the expression of nephrin was increased. The mean systolic pressure and UAER in group C were significantly lower than those in group B (P <0.05) and nephrin expression was decreased. Conclusion: Eplerenone can reduce aldosterone-induced podocyte injury by changing nephrin expression level in glomerular podocytes.