Glomerular proteoglycans in diabetic nephropathy

糖尿病肾病最典型的变化是在肾小球细胞外基质中观察到的，包括肾小球基底膜（GBM）增厚和系膜基质增加。其中，硫酸乙酰肝素蛋白聚糖（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，采用抗HS-PG抗体对糖尿病肾病患者肾活检组织中细胞外基质的变化进行了研究。通过间接免疫荧光法，在结节性肾小球硬化和肾病综合征患者的肾标本中观察到抗HS-PG染色强度明显降低。与正常对照样品结果相比，在硬化性肾小球的系膜中观察到IV型胶原增加。免疫电镜下，HS-PG主要分布于GBM的内、外板层，而IV型胶原则分布于整个GBM。在糖尿病患者中，观察到GBM的稀有内层和外层中的HS-PG损失。IV型胶原分布在增厚的GBM的所有层中，并且与对照相比，单位面积的免疫金密度较低。然而，考虑到与对照组相比，糖尿病患者的GBM增厚了三到五倍。与IV型胶原蛋白反应的金颗粒的绝对数量增加。这些研究结果表明，免疫反应性HS-PG和IV型胶原蛋白的浓度的变化可能是相关的电荷损失以及GBM的大小选择性，如在糖尿病肾病与蛋白尿相关。

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.