Glomerular basement membrane permeability factor in minimal change nephrotic syndrome

微小病变型肾病综合征（MCNS）是儿童肾病综合征中最常见的一种。然而，MCNS的发病机制仍不清楚。一些研究者提出MCNS是免疫介导的疾病。Shalhoub假设MCNS患者的淋巴细胞产生一种淋巴因子，导致肾小球基底膜（GBM）通透性增加，导致蛋白尿和肾病综合征，检测了MCNS患儿外周血单核细胞培养上清液增加GBM通透性的能力和对GBM阴离子位点的影响。将MCNS患者伴刀豆球蛋白A刺激的外周血单个核细胞培养上清液注入正常大鼠肾动脉。输注导致GBM阴离子位点显著减少，尿白蛋白排泄显著增加。这些结果表明，刺激MCNS的外周血单个核细胞导致可溶性物质的释放，减少GBM中的聚阴离子，增加GBM的通透性。VPF增加血管的液体渗透性。北方印迹分析显示，人外周血单个核细胞和肾小球系膜细胞表达VPF mRNA。在人肾小球系膜细胞中也检测到VPF蛋白。大鼠输注VPF后，尿白蛋白排泄量呈剂量依赖性增加。这些结果表明，系膜细胞和外周血单个核细胞产生VPF和VPF从这些细胞释放诱导白蛋白尿MCNS。

Minimal change nephrotic syndrome(MCNS)is the most common form of nephrotic syndrome in children. However, the pathogenesis of MCNS remains unknown. Several investigators have been proposed suggesting that MCNS is immune-mediated disorder. Shalhoub postulated that lymphocytes in patients with MCNS produce a lymphokine that causes increased permeability of the glomerular basement membrane(GBM), resulting in proteinuria and nephrotic syndrome.Supernatants of peripheral blood mononuclear cell culture from children with MCNS were tested for their ability to increase GBM permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS were infused into the renal arteries of normal rats. Infusion caused a significant reduction of anionic sites in the GBM and a significant increase in urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS results in liberation of soluble substances which reduce polyanions in the GBM and increase GBM permeability.Recently vascular permeability factor(VPF)has been purified from human lymphoma line. VPF increases fluid permeability from blood vessels. Northern blot analysis revealed that human peripheral blood mononuclear cells and glomerular mesangial cells expressed VPF mRNA. VPF protein was also detected in human mesangial cells. VPF infusion into rats resulted in a dosedependent increase in urinary albumin excretion. These findings indicate that mesangial cells and peripheral blood mononuclear cells produce VPF and VPF released from these cells induces albuminuria in MCNS.