Administration of dexamethasone induces proteinuria of glomerular origin in mice
Administration of dexamethasone induces proteinuria of glomerular origin in mice
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DOI：
10.1053/ajkd.1998.v31.pm9506681
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发表时间：
1998-03-01
影响因子：
13.2
通讯作者：
Lee, WH
中科院分区：
文献类型：
--
作者：
Chen, A;Sheu, LF;Lee, WH
据报道，在少数肾小球肾炎患者中，糖皮质激素的使用可加重蛋白尿。这种影响尚未得到很好的认识，这种现象的发病机制仍有待澄清。在这项研究中，我们观察到，地塞米松（0.5mg/kg体重）能够在小鼠中诱导明显的蛋白尿，从第5天开始并持续19天的持续时间，四分之一的小鼠还从第12天开始间歇性地出现轻微的血尿。地塞米松处理的小鼠中的肾损伤，其在第23天被杀死，特征为轻度系膜扩张、深层皮质肾小球节段性或整体性玻璃样变性/硬化以及局灶性肾小管变化。在任何小鼠中均未观察到肾小球炎性细胞浸润或增殖性病变。肾小球的超微结构特征包括肾小球系膜增宽，其特征为系膜基质增加，扩张的系膜通道充满轻微的电子致密物质或系膜溶解样外观，显示胞浆内微囊充满电子透明物质，以及支持内皮细胞、红细胞和足细胞损伤的证据。免疫荧光研究显示，肾小球IgG、伊加、IgM和纤维蛋白原沉积增强（与正常对照小鼠相比，P < 0.001），但在任何地塞米松处理的小鼠中均未发现肾小球C3沉积。电荷分析显示地塞米松处理的小鼠肾小球簇的阴离子性质没有受损。此外，地塞米松诱导的蛋白尿可通过低分子量肝素治疗大大减弱，尽管血管紧张素转换酶抑制剂不能减少。这些实验的数据表明，大剂量的糖皮质激素具有潜在的肾毒性。大小依赖性通透性的改变可能是地塞米松诱导的蛋白尿的主要原因。然而，肾小球超滤的作用可能只是部分参与了地塞米松诱导的小鼠肾小球病的发病机制。(C)1998年由国家肾脏基金会，公司。
The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration, One fourth of mice also intermittently presented with slight hematuria beginning on day 12, Renal lesions in the dexamethasone-treated mice, which were killed an day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme Inhibitor, Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice. (C) 1998 by the National Kidney Foundation, Inc.