Figueira Miriam F, Castiglione Raquel C, de Lemos Barbosa Carolina M, Ornellas Felipe M, da Silva Feltran Geórgia, Morales Marcelo M, da Fonseca Rodrigo N, de Souza-Menezes Jackson
Laboratório Integrado de Ciências Morfofuncionais, Núcleo em Ecologia e Desenvolvimento Socioambiental de Macaé, Universidade Federal do Rio de Janeiro, Macaé, Rio de Janeiro, Brazil.
Laboratório de Fisiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Physiol Rep. 2017 Jul;5(13). doi: 10.14814/phy2.13335.
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC-5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC-5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low-molecular-weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats.
糖尿病肾病（DN）发生于约40%的糖尿病患者中。蛋白尿是DN的主要特征，其发生是由于肾小球毛细血管壁通透性增加和/或近端小管内吞作用减弱。本研究的目的是评估1型糖尿病大鼠近端小管和肾皮质的肾功能以及巨膜蛋白、立方蛋白、囊性纤维化跨膜传导调节因子（CFTR）和氯离子通道蛋白5（ClC-5）的表达。雄性Wistar大鼠被随机分为对照组（CTRL）和糖尿病组（DM），为期4周。通过计算溶质清除率和排泄分数，评估24小时尿液样本中的肾功能。分别使用实时聚合酶链反应和蛋白质印迹技术，测定肾近端小管和皮质中ClC-5、CFTR、巨膜蛋白和立方蛋白的RNA和蛋白质含量。结果显示，DM组的肌酐清除率以及蛋白质、白蛋白和转铁蛋白的尿排泄量均高于CTRL组。此外，糖尿病动物的肾皮质和近端小管显示出巨膜蛋白、立方蛋白、ClC-5和CFTR（内吞装置的关键成分）表达下调。这些数据表明糖尿病大鼠肾脏近端小管低分子量内吞作用和蛋白质肾小球滤过功能存在障碍。
