Bellisola G, Guidi G C, Cinque G, Galassini S, Liu N Q, Moschini G, Rugiu C, Lupo A
Dipartimento di Chimica Clinica, Laboratorio COC Valeggio sul Mincio, Università di Verona, Italia.
J Trace Elem Med Biol. 1996 Sep;10(3):189-96. doi: 10.1016/S0946-672X(96)80032-0.
The abnormal proliferation of mesangial cells with IgA deposition in the glomeruli characterizes primitive mesangial glomerulonephritis (IgA nephropathy, IgAN); this disease reduces the normal renal parenchyma while renal function becomes progressively impaired. The possible role of selenium has never been considered in evaluating factors involved in the pathogenesis of IgAN. In this work we compared the Se status of 14 IgAN patients (8 with normal renal function, IgAN NRF; 6 with impaired renal function, IgAN IRF) to that of 14 normal individuals (CG NRF) before and after an oral supplementation with selenite (0.13 mol Se/kg b.w./day for 60 days). The following indices of Se status were measured: Se in plasma and urine samples by PIXE; glutathione peroxidase activity in the cytosol of platelets (PLTs-GSH-Px) and of erythrocytes (RBCs-GSH-Px). Both concentrations and activities of plasma glutathione peroxidase (pl-GPx), a selenoenzyme mainly synthesized in and secreted by the kidney, were measured in plasma samples and results compared among groups. IgAN patients showed lower pl-Se and lower activities of selenoenzymes than normal controls before Se supplementation (p < 0.001). These findings suggest that an impaired Se status coexisted with the proliferation of mesangial cells in patients. Selenite induced PLTs-GSH-Px activity in all individuals (p < 0.001), but no variation was observed in RBCs-GSH-Px activity or in the concentration of pl-GPx in the plasma. On the other hand, selenium induced pl-GPx activity in CG NRF (p < 0.001) and in IgAN NRF (p < 0.01), but poorly stimulated pl-GPx activity in IgAN IRF (p = n.s.). However, only 17% and 25% of the pl-GPx activity of normal controls was measured in the plasma of IgAN IRF and IgAN NRF patients, respectively (p < 0.001). In conclusion, selenite only partially restored a normal Se status in patients whose low pl-GPx activity probably reflects an impaired synthesis of this protein as a consequence of reduced normal functioning of the parenchyma in kidneys affected by IgA nephropathy.
肾小球系膜细胞异常增殖并伴有IgA沉积于肾小球是原发性系膜增生性肾小球肾炎（IgA肾病，IgAN）的特征；这种疾病会减少正常肾实质，同时肾功能会逐渐受损。在评估IgAN发病机制的相关因素时，从未考虑过硒的可能作用。在这项研究中，我们比较了14例IgAN患者（8例肾功能正常，IgAN NRF；6例肾功能受损，IgAN IRF）与14例正常个体（CG NRF）在口服亚硒酸盐（0.13 μmol Se/kg体重/天，持续60天）前后的硒状态。测量了以下硒状态指标：通过PIXE测定血浆和尿液样本中的硒；血小板（PLTs-GSH-Px）和红细胞（RBCs-GSH-Px）胞质溶胶中的谷胱甘肽过氧化物酶活性。在血浆样本中测量了血浆谷胱甘肽过氧化物酶（pl-GPx）的浓度和活性，pl-GPx是一种主要在肾脏合成并分泌的含硒酶，并对各组结果进行了比较。在补充硒之前，IgAN患者的血浆硒（pl-Se）和含硒酶活性低于正常对照组（p < 0.001）。这些发现表明患者体内硒状态受损与系膜细胞增殖并存。亚硒酸盐可诱导所有个体的PLTs-GSH-Px活性（p < 0.001），但未观察到RBCs-GSH-Px活性或血浆中pl-GPx浓度的变化。另一方面，硒可诱导CG NRF（p < 0.001）和IgAN NRF（p < 0.01）的pl-GPx活性，但对IgAN IRF的pl-GPx活性刺激较弱（p = 无统计学意义）。然而，在IgAN IRF和IgAN NRF患者的血浆中，分别仅测得正常对照组pl-GPx活性的17%和25%（p < 0.001）。总之，亚硒酸盐仅部分恢复了患者的正常硒状态，其低pl-GPx活性可能反映了受IgA肾病影响的肾脏实质正常功能降低导致该蛋白合成受损。
