Glomerular proteoglycans in diabetic nephropathy

绝热肾病最典型的变化见于肾小球细胞外基质，包括肾小球基底膜（GBM）增厚和系膜基质增加。其中，硫酸肝素蛋白聚糖（HS-PG）的丢失被认为在糖尿病肾病的病因学中起重要作用。为了阐明HS-PG在糖尿病肾病中的作用，我们利用针对HS-PG的抗体研究了糖尿病肾病患者肾活检组织中细胞外基质的变化。通过间接免疫荧光，在结节性肾小球硬化和肾病综合征患者的肾脏标本中观察到抗hs - pg染色强度明显降低。与正常对照样本相比，在硬化肾小球系膜中观察到IV型胶原蛋白的增加。采用免疫-金-金技术的免疫电镜观察发现，HS-PG分布于外、内筋膜，而IV型胶原分布于正常对照GBM的整个宽度。在糖尿病患者中，观察到GBM内部和外部椎板中HS-PG的丢失。IV型胶原分布于增厚的GBM各层，单位面积免疫金密度较对照组低。然而，考虑到糖尿病患者的GBM增厚是对照组的三到五倍，与IV型胶原反应的金颗粒的绝对数量增加。这些发现表明，免疫反应性HS-PG和IV型胶原浓度的改变可能与GBM的电荷损失和大小选择性有关，正如在蛋白尿相关的糖尿病肾病中观察到的那样。

The changes most characteristic of diabatic nephropathy are observed in the glomerular extracellular matrices and, include thickening of the glomerular basement membrane(GBM)and increase in the mesangial matrix. Among these, the loss of heparan sulfate proteoglycan(HS-PG)is believed to play an important role in the etiology of diabetic nephropathy. In order to clarify the role of HS-PG in diabetic nephropathy, changes in extracellular matrices was studied in renal biopsy tissues obtained from patients with diabetic nephropathy employing antibodies directed against HS-PG. By indirect immunofluorescence, a marked reduction in the intensity of staining with anti-HS-PG was observed in renal specimens from patients with nodular glomerulosclerosis and nephrotic syndrome. An increase compared to normal control sample findings in type IV collagen was observed in the mesangium of sclerosing glomeruli. By immunoelectron microscopy employing immuno-gold-gold technique, HS-PG was distributed in the lamina rara interna and externa while type IV collagen was distributed throughout the whole width of the GBM in normal controls. In diabetic patients, a loss of HS-PG both in the lamina rara interna and externa of the GBM was observed. The type IV collagen was distributed in all the layers of the thickened GBM, and the immunogold density per unit area was less as compared to the control. However, taking account for the three to five times thickening of the GBM in diabetes as compared to controls, . the absolute number of gold particles reactive with type IV collagen was increased. These findings suggest that the alterations in the concentration of immunoreactive HS-PG and type IV collagen may be relevant in the losses of charge as well as size-selectivities of the GBM, as observed in diabetic nephropathy associated with proteinuria.