肾小球足细胞裂隙膜蛋白Podocin的变化与氧化应激反应

Podocin in glomerular podocyte slit diaphragm and oxidative stress

目的探讨氧化应激反应在肾小球足细胞裂隙膜分子屏障损伤中的作用。方法32只体重180～220g的♂SD大鼠按阿霉素给药剂量随机分成4组。于给药第3周末测尿蛋白的变化,同时处死大鼠取肾皮质检测氧化应激指标及肾小球Podocin蛋白的分布及半定量。结果①阿霉素组大鼠24h尿蛋白量及肾皮质丙二醛(MDA)量高于正常对照组,超氧化物歧化酶(SOD)量低于正常对照组,尤以中剂量组变化最明显。②正常对照组大鼠Podocin沿肾小球基底膜呈深褐色连续、线形分布;在中剂量组呈淡褐色点状或短线条状分布;量化分析显示,阿霉素组肾小球Podocin免疫组化分数明显低于正常对照组,尤以中剂量组最显著。③肾小球Podocin蛋白免疫组化分数与肾皮质MDA浓度呈负相关,与肾皮质SOD浓度呈正相关。结论蛋白尿的发生与肾小球足细胞裂隙膜蛋白Podocin的变化密切相关;肾小球足细胞裂隙膜蛋白Podocin的减少或缺失与以脂质过氧化反应为主的氧化应激反应密切相关。

Objective To explore the effect of oxidative stress on the injury of glomerular podocyte slit diaphragm molecular barrier. Methods Thirty-two male Spraque-Dawley （SD） rats were randomly divided into four groups by the dosage of adriamycin （ADR） injection. Three weeks later proteinuria was measured and all rats were killed. The renal cortex was taken in order to detect oxidative stress reaction and the expression of podocin. Results ① Compared with control group, the levels of malondialdehyde （MDA） in renal cortex and 24-hour urinary protein were increased, the levels of supemxide dismutase （SOD） was decreased in ADR groups, especially in medium close group （P 〈 0. 05）. ② In control group, Podocin staining was a sable linear-like pattern along the capillary loops of glomerulus;In medium dose group, Podocin staining was a light tan discontinuous punctiform or short linear-like pattern along the capillary loops of glomerulus ; Compared with control group, the score of Podocin immunohistochemical （ IHC ） staining was decreased in ADR groups, especially in medium dose group （ P 〈 0. 05 ）. ③ There were some significant negative correlations between the score of Podocin IHC staining and the levels of MDA in renal cortex. There were some significant positive correlations between the score of Podocin IHC staining and the levels of SOD in renal cortex. Conclusion ① There is close relationship between podocin and the development of proteinuria. ② There is significant correlations between the reduction of podocin in glomerular podocyte slit diaphragm and oxidative stress reaction, especially lipid peroxidation.