Sargin Ayse Kose, Can Belgin, Turan Belma
Department of Histology-Embriology, Faculty of Medicine, Ankara University, Ankara, Turkey.
Mol Cell Biochem. 2014 May;390(1-2):41-9. doi: 10.1007/s11010-013-1953-7. Epub 2013 Dec 29.
High glucose and increased oxidative stress levels are the known important mediators of diabetic nephropathy. However, the effects of these mediators on tissue damage basically due to extracellular matrix expansion in mesangial cells have yet to be fully examined within the context of early stage diabetic nephropathy. In this study, we attempted to characterize changes in mesangial cells of streptozotocin-induced diabetic rats with a comparative investigation of kidney tissue by using different microscopy techniques. The serum levels of urea and creatinine of diabetic rats, as biomarkers of kidney degeneration, decreased significantly compared to those of age-matched controls. In diabetic rats, there are increased malondialdehyde and oxidized-glutathione levels as well as reduced-glutathione and glutathione-peroxidase activity levels in renal tissue compared to those of the controls. By using light and electron microscopies, we showed that there were marked thickening in Bowman's membrane and glomerular capillary wall, increased amount of extracellular matrix often occupying Bowman's space, degenerations in tubules, an increased number of mesangial cells in the network of glomerular capillary walls, and increased amount of lipid accumulation in proximal tubules in the renal tissue of diabetic rats. Our confocal microscopy data confirmed also the presence of irregularity and widened in glomerular capillaries, their attachment to the Bowman's capsule, degenerated heterochromatin, thickening in foci of glomerular basement membrane, and marked increase in mesangial cells. These results suggest that a detailed structural investigation of kidney tissue provides further information on the important role of mesangial cells in pathogenesis of diabetic nephropathy.
高血糖和氧化应激水平升高是糖尿病肾病已知的重要介质。然而,在早期糖尿病肾病的背景下,这些介质对主要由于系膜细胞外基质扩张所致组织损伤的影响尚未得到充分研究。在本研究中,我们试图通过使用不同的显微镜技术对肾脏组织进行比较研究,来描述链脲佐菌素诱导的糖尿病大鼠系膜细胞的变化。与年龄匹配的对照组相比,作为肾脏退化生物标志物的糖尿病大鼠血清尿素和肌酐水平显著降低。与对照组相比,糖尿病大鼠肾组织中丙二醛和氧化型谷胱甘肽水平升高,而还原型谷胱甘肽和谷胱甘肽过氧化物酶活性水平降低。通过光学显微镜和电子显微镜观察,我们发现糖尿病大鼠肾组织中鲍曼膜和肾小球毛细血管壁明显增厚,占据鲍曼间隙的细胞外基质增多,肾小管退化,肾小球毛细血管壁网络中的系膜细胞数量增加,近端小管中脂质蓄积量增加。我们的共聚焦显微镜数据也证实了肾小球毛细血管存在不规则和增宽、它们与鲍曼囊的附着、异染色质退化、肾小球基底膜病灶增厚以及系膜细胞显著增加。这些结果表明,对肾脏组织进行详细的结构研究可进一步了解系膜细胞在糖尿病肾病发病机制中的重要作用。