Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria - A model of steroid-resistant nephrosis sensitive to radical scavenger therapy
Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria - A model of steroid-resistant nephrosis sensitive to radical scavenger therapy
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DOI：
10.1016/s0002-9440(10)65359-x
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发表时间：
1999-04-01
影响因子：
6
通讯作者：
Kerjaschki, D
中科院分区：
文献类型：
--
作者：
Binder, CJ;Weiher, H;Kerjaschki, D
局灶节段性肾小球硬化症是一种类固醇抵抗性肾小球疾病，其特征是足突扁平和大量蛋白尿。在通过逆转录病毒插入使 Mpv17 基因失活的小鼠（Mpv17-/- 小鼠）中发现类似的疾病自发发生。这里提供的证据表明，该小鼠模型中的肾小球损伤是由于在 Mpv17-/- 小鼠的分离肾小球中发现的氧自由基的过量产生和脂质过氧化加合物的积累所致。Mpv17-/- 小鼠中肾小球疾病的发展受到氧自由基清除剂（二硫甲基脲）和脂质过氧化（普罗布考）的抑制，但不能通过类固醇治疗来抑制。尽管蛋白尿 Mpv17-/- 小鼠的肾小球聚阴离子大大减少，但通过抗氧化治疗得以保留。这些结果表明，Mpvl7-/-小鼠的肾小球疾病符合类固醇抗性局灶节段性肾小球硬化的模型，并且使用氧自由基和脂质过氧化清除剂的实验疗法可有效改善肾小球损伤。
Focal segmental glomerulosclerosis is a steroid-resistant glomerular disease characterized by foot process flattening and heavy proteinuria, A similar disease was found to occur spontaneously in mice in which the Mpv17 gene was inactivated by retroviral insertion (Mpv17-/- mice). Here evidence is provided that glomerular damage in this murine model is due to overproduction of oxygen radicals and accumulation of lipid peroxidation adducts that were found in isolated glomeruli of Mpv17-/- mice, The development of glomerular disease in Mpv17-/- mice was inhibited by scavengers of oxygen radicals (dithiomethylurea) and lipid peroxidation (probucol), but not by steroid treatment. Although the glomerular polyanion was greatly reduced in proteinuric Mpv17-/- mice, it was preserved by antioxidative therapy. These results indicate that the glomerular disease in Mpvl7-/- mice qualifies as a model of steroid-resistant focal segmental glomerulosclerosis and that experimental therapies with scavengers of oxygen radicals and lipid peroxidation efficiently ameliorate glomerular damage.