Functional and structural alterations of the glomerular permeability barrier in experimental galactosemia.

Functional and structural alterations of the glomerular permeability barrier in experimental galactosemia.
复制标题

实验性半乳糖血症肾小球通透性屏障的功能和结构改变。

DOI:
10.1038/ki.1991.140
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发表时间:
1991
影响因子:
19.6
通讯作者:
Hostetter,TH
Hostetter,TH
中科院分区:
医学1区
文献类型:
--
作者:
Daniels,BS;Hostetter,TH

文献摘要

被引文献

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实验性半乳糖血症肾小球通透性屏障的功能和结构改变。实验性半乳糖血症,诱导喂养大鼠富含半乳糖的饮食,再现了许多神经和眼部并发症的糖尿病,并诱导蛋白质糖化和多元醇的积累。为了探索这些生化异常在肾小球损伤发病机制中的作用,将成年雄性Sprague-Dawley大鼠置于50%半乳糖或50%葡萄糖饮食中。两个月后,半乳糖喂养的大鼠表现出蛋白质,白蛋白和IgG的排泄率升高。在半乳糖补充饮食的大鼠中,肾小球上皮细胞的起泡和气球样变明显。肾小球的形态学评价显示肾小球上皮细胞的分数和绝对体积增加,但肾小球和系膜体积,基底膜厚度和上皮足突宽度在两种饮食中相似。半乳糖喂养大鼠肾小球基底膜的糖化增加。肾小球微穿刺显示两种饮食的肾小球压力和流速相似。抑制醛糖还原酶对半乳糖诱导的蛋白尿无影响。这些结果表明,生化异常,如蛋白糖化可能是重要的糖尿病肾病肾小球选择性渗透性改变的发病机制。
Functional and structural alterations of the glomerular permeability barrier in experimental galactosemia. Experimental galactosemia, induced by feeding rats a galactose enriched diet, reproduces many of the neural and ocular complications of diabetes and induces protein glycation and polyol accumulation. To explore the role of these biochemical abnormalities in the pathogenesis of glomerular injury, adult male Sprague-Dawley rats were placed on either a 50% galactose or 50% glucose diet. After two months, galactose fed rats exhibited elevated excretory rates of protein, albumin, and IgG. Blebbing and ballooning of the glomerular epithelial cells were apparent in rats on the galactose supplemented diet. Morphometric evaluation of the glomeruli revealed an increase in the fractional and absolute volume of the glomerular epithelial cells, but glomerular and mesangial volume, basement membrane thickness, and epithelial foot process width were similar on the two diets. Glycation of the glomerular basement membrane was increased in the galactose fed rats. Glomerular micropuncture revealed similar glomerular pressures and flow rates on the two diets. Aldose reductase inhibition had no effect on galactose induced proteinuria. These results suggest that biochemical abnormalities such as protein glycation may be important in the pathogenesis of altered glomerular permselectivity in diabetic nephropathy.