Herrmann Annika, Tozzo Effie, Funk Jürgen
Non-clinical Drug Safety and Metabolic Diseases Departments, F. Hoffmann-La Roche Ltd., Switzerland.
Exp Toxicol Pathol. 2012 Jan;64(1-2):45-9. doi: 10.1016/j.etp.2010.06.004. Epub 2010 Jun 29.
Glomerular visceral epithelial cells or podocytes are crucial for glomerular function and podocyte damage has been shown to be inevitably involved in glomerulopathies. Podocytes react to injury in a stereotypic manner. Accompanying morphologic changes is altered expression of intermediate filaments. Desmin is strongly upregulated in injured podocytes. Here we show, that semi-automated quantitative image analysis of desmin immunoreactivity in glomerula is a valid and sensitive marker for acute podocyte and thus glomerular damage in the puromycin aminonucleoside nephrosis (PAN) model in the rat with the potential of an efficacy marker in animal disease models as well as a toxicity marker for podocyte injury. Additionally, a panel of acknowledged urinary kidney biomarkers was evaluated for utility in the PAN model.
肾小球脏层上皮细胞或足细胞对肾小球功能至关重要,且已表明足细胞损伤不可避免地参与肾小球疾病。足细胞以刻板的方式对损伤做出反应。伴随形态学变化的是中间丝表达的改变。结蛋白在受损足细胞中强烈上调。在此我们表明,肾小球中结蛋白免疫反应性的半自动定量图像分析是大鼠嘌呤霉素氨基核苷肾病(PAN)模型中急性足细胞损伤以及肾小球损伤的有效且敏感的标志物,具有作为动物疾病模型中的疗效标志物以及足细胞损伤毒性标志物的潜力。此外,还评估了一组公认的尿肾生物标志物在PAN模型中的效用。