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长期高脂肪饮食摄入诱导雌性大鼠肾脏形态和功能的时程紊乱。

Time-course morphological and functional disorders of the kidney induced by long-term high-fat diet intake in female rats.

机构信息

Renal Function Laboratory, Campinas State University, UNICAMP, Campinas, São Paulo, Brazil.

出版信息

Nephrol Dial Transplant. 2013 Oct;28(10):2464-76. doi: 10.1093/ndt/gft304.

DOI:10.1093/ndt/gft304
PMID:24078639
Abstract

BACKGROUND

Evidence is emerging that highlights the far-reaching consequences of a high-fat diet (HFD) on kidney morphology and function disorders.

METHODS

The present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared with the appropriate gender and age-matched animals. We evaluated the kidney expression of angiotensin type II receptor and fibrotic and epithelial-to-mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical and histological techniques, in parallel with kidney function.

RESULTS

In the current study, the time-course HFD-treated group showed, by immunoblotting and immunohistochemical analysis, an early time-course increase in the expression of transforming growth factor β-1 (TGFβ-1) in the entire kidney of HFD-treated rats, compared with that observed in the control group. Simultaneously, the study shows a transient increase in the expression of ZEB2 in the HFD whole kidney accompanied by a fall in the E-cadherin expression and increased collagen and fibronectin deposition. A pronounced decrease in fractional urinary sodium excretion was also demonstrated in the long-term HFD-treated rats. The decreased FENa(+) was accompanied by a fall in FEPNa(+) and FEPPNa(+), which occurred in association with significantly decreased CCr and, certainly on the sodium-filtered load. The reduction in the glomerular filtration rate (GFR) occurred in parallel to proteinuria and glomerular desmin overexpression.

CONCLUSIONS

The results of the current study suggest that podocyte injury in parallel with observed proteinuria and evidence of EMT transformation are associated with long-term loss of kidney function and renal sodium and water retention.

摘要

背景

有证据表明,高脂肪饮食(HFD)对肾脏形态和功能障碍的影响深远。

方法

本研究对 3、5、7 和 9 周龄的 HFD 雌性大鼠与相应性别和年龄匹配的动物进行了比较。我们通过免疫印迹、免疫组织化学和组织学技术评估了肾脏血管紧张素 II 受体和纤维化及上皮-间充质转化(EMT)标志物的表达,并与肾功能平行评估。

结果

在本研究中,通过免疫印迹和免疫组织化学分析,HFD 处理组在整个肾脏中 TGFβ-1 的表达在早期呈时间依赖性增加,与对照组相比观察到的表达。同时,该研究表明 ZEB2 在 HFD 整个肾脏中的表达短暂增加,同时 E-钙粘蛋白表达下降,胶原和纤维连接蛋白沉积增加。在长期 HFD 处理的大鼠中也明显证明了尿钠排泄分数的降低。FENa(+) 的减少伴随着 FEPNa(+) 和 FEPPNa(+) 的下降,这与 CCr 的显著下降有关,当然也与钠滤过负荷有关。肾小球滤过率(GFR)的下降与蛋白尿和肾小球 desmin 过表达平行发生。

结论

本研究的结果表明,足细胞损伤与观察到的蛋白尿和 EMT 转化的证据有关,与长期肾功能丧失和肾脏钠水潴留有关。

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