Alteration of glomerular anionic sites and expression of renal heparanase in respiratory syncytial virus nephropathy in rats

Abstract

Objective To observe the alteration of glomerular anionic sites and renal heparanase(Hpa)expression in respiratory syncytial virus(RSV) nephropathy in rats, and to investigate the role of Hpa in the pathogenesis of proteinuria in RSV nephropathy. Methods Twenty-five Sprague-Dawley(SD) rats were inoculated with 6×106 plaque forming units(PFU) RSV and were sacrificed on days 4, 8, 14 and 28 post-inoculation(RSV4, RSV8, RSV14 and RSV28 group). Five normal SD rats served as normal control.The proteinuria and serum parameters were measured.Glomerular anionic sites were measured by histochemical electron microscopy.The expression of Hpa in kidney was determined by immunohistochemical staining.The relationship between the expression level of Hpa and the quantity of 24-hour urine protein was studied. Results After inoculation, the proteinuria increased, especially in RSV14 group.The 24-hour urine protein of RSV14 group, RSV8 group, RSV28 group, RSV4 group and normal group were (30.9860±3.3464) mg, (15.3212±1.2249) mg, (13.9193±2.1409) mg, (11.5857±1.5705) mg, (3.9780±0.6224) mg, respectively.The serum albumin of RSV14 group decreased.The anionic sites of glomerular basement membrane(GBM) decreased in RSV nephropathy.The number of anionic sites per 1000 nm GBM of RSV14 group, RSV8 group, RSV28 group, RSV4 group and normal control group were 12.0000±1.5811, 14.0000±1.0000, 14.6000±1.1401, 16.8000±0.8366 and 21.2000±1.3038, respectively.Hpa in glomeruli couldn't be detected in normal rats.Glomerular Hpa expression was up-regulated in RSV nephropathy.The expression of glomerular Hpa of RSV14 group, RSV8 group, RSV28 group and RSV4 group were 0.6622±0.1145, 0.5511±0.0257, 0.3524±0.0296 and 0.4521±0.0087, respectively.The expression level of Hpa in RSV8 group and RSV14 group was higher than that in RSV4 group and RSV28 group.There was a linear positive correlation between the expression level of glomerular Hpa and the quantity of 24-hour urine protein(r=0.783, P<0.05). Conclusions The increased expression of glomerular Hpa in RSV nephropathy of rats leads to loss of the glomerular anionic sites and damage of the electrostatic barrier of GBM, which promote the proteinuria. Key words: Respiratory syncytial virus; Minimal change nephrotic syndrome; Glomerular anionic site; Heparanase; Rat