Adriamycin Alters Glomerular Endothelium to Induce Proteinuria
Adriamycin Alters Glomerular Endothelium to Induce Proteinuria
复制标题
DOI：
10.1681/asn.2007111205
复制
发表时间：
2009-01-01
影响因子：
13.6
通讯作者：
Haraldsson, Borje
中科院分区：
文献类型：
--
作者：
Jeansson, Marie;Bjorck, Karin;Haraldsson, Borje
肾病综合征的病理生理学基础是几种遗传性足细胞病，变得越来越清楚，损伤的机制，导致获得性形式的这种疾病还没有得到很好的理解。我们使用阿霉素诱导的蛋白尿小鼠模型来探讨这些机制。我们估计了FITC-Ficolls、白蛋白和中性白蛋白在冷却、分离、灌注肾脏（cIPK）中的原位清除率。阿霉素治疗导致半径大于20埃的白蛋白和Ficoll的清除分数显著增加。中性白蛋白（33.4埃）和类似大小的Ficoll表现彼此相似。此外，阿霉素导致肾小球屏障的电荷密度和大小选择性的显着损失。肾小球内皮表面层的厚度（即，或糖萼）仅为正常动物的20%。最后，几种蛋白多糖在离体肾小球中下调。总之，阿霉素可能通过下调蛋白多糖的合成使肾小球糖萼变薄，并改变肾小球电荷和大小的选择性。这些数据表明，肾小球内皮细胞可能在蛋白尿性肾病的发病机制中发挥作用。
The pathophysiology underlying the nephrotic syndrome is becoming clear for several inherited podocytopathies; the mechanisms of injury that lead to the acquired forms of this disease are not well understood. We explored these mechanisms using the mouse model of adriamycin-induced proteinuria. We estimated the fractional clearances for FITC-Ficolls, albumin, and neutral albumin in cooled, isolated, perfused kidneys (cIPK) in situ. Treatment with adriamycin led to a significant increase in the fractional clearance of albumin and of Ficoll with radii larger than 20 angstrom. Neutral albumin (33.4 angstrom) and similarly sized Ficoll behaved similarly to each other. In addition, adriamycin led to a significant loss of charge density and size selectivity of the glomerular barrier. The thickness of the glomerular endothelial surface layer (i.e., or the glycocalyx) in adriamycin-treated animals was only 20% of that in normal animals. Finally, several proteoglycans were downregulated in isolated glomeruli. In summary, adriamycin thins the glomerular glycocalyx, perhaps by downregulating proteoglycan synthesis, and alters glomerular charge- and size selectivity. These data suggest that the glomerular endothelium may play a role in the pathogenesis of proteinuric renal diseases.