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Studies of glomerular basement membrane permeability factor in minimal change nephrotic syndrome

微小病变肾病综合征肾小球基底膜通透性因子的研究

基本信息

批准号：
63570425
负责人：
TOMIZAWA Shigeru
金额：
$ 1.34万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

The etiology of minimal change nephrotic syndrome(MCNS) is obscure. Several investigators have presumed that vascular permeability factor(VPF) derived from lymphocyte cultures in MCNS might be related to massive proteinuria. We already demonstrated that VPF was produced by T-lymphocytes from patients with MCNS. Furthermore, the infusion of T-lymphocyte culture supernatants from patients with MCNS into the left renal artery of rats, induced not only significant proteinuria in the rat urine but also a reduction of anionic sites in the glomerular basement membrane of the kidney in the hats. In order to determine the identity of T-lymphocyte subset in MCNS which release VPF, VPF assay of the culture supernatant of T-lymphocyte, CD4^+ cell or CD8^+ cell enriched fraction was performed. T-lymphocytes were purified by passage over a nylon wool column and separated to either CD4^+ cell or CD8^+ cell enriched fractions with monoclonal antibodies (anti-OKT4 and anti-OKT8 antibody) and a rabbit c … More omplement. VPF activity was found in either T-lymphocyte or CD4^+ cell enriched culture-supernatant. Moreover, its activity has not been inhibited by either anti-IL1 or anti-IL2 antibody. These results suggest that VPF might be different from lymphokines such as IL1 or IL2 and be produced by CD4^+ cells. Further studies are needed to clarify the correlations between VPF production of CD4^+ cells and massive proteinuria in MCNS.Next, it is reported that pI changes of serum and urine from nephrotic patients will be one of causes of protein excretion. We purified albumin from urine and investigated the pI and glomerul; basement membrane(GBM) permeability of rat kidney by infusing of the albumin. As the results, less anionic albumin was detected in the urine from MCNS patients. After infusion of the less anionic albumin to the rat kidney, the negative charge of the rat GBM was reduced and increased protein excretion. From these results, it is presumed that less anionic albumin will neutralized the negative charge of GBM, and will enhance the protein permeability. This will be one of the mechanism of protein excretion. Less

微小病变型肾病综合征(MCNS)的病因尚不清楚。一些研究人员推测，来自MCNS淋巴细胞培养的血管通透性因子(VPF)可能与大量蛋白尿有关。我们已经证明VPF是由MCNS患者的T淋巴细胞产生的。此外，将MCNS患者的T淋巴细胞培养上清液注入大鼠左肾动脉，不仅引起大鼠尿蛋白尿，而且使HATS中肾小球基底膜上的阴离子部位减少。为了确定MCNS中释放VPF的T淋巴细胞亚群的特性，对T淋巴细胞培养上清液、CD4^+细胞或CD8^+细胞的浓缩部分进行了VPF检测。用抗OKT4和抗OKT8的单抗和兔c…分离纯化的T淋巴细胞。更多的充实。富含VPF活性的T淋巴细胞和CD4~+细胞培养上清液中均有VPF活性。此外，其活性未被抗IL1或抗IL2抗体所抑制。这些结果提示VPF可能不同于IL-1或IL-2等淋巴因子，而是由CD_4~+细胞产生。CD4~+细胞产生VPF与MCNS大量蛋白尿的相关性有待进一步研究。此外，据报道，肾病患者血、尿PI的变化将是蛋白排泄的原因之一。从大鼠尿液中提纯白蛋白，观察其对大鼠肾脏PI和肾小球基底膜(GBM)通透性的影响。结果表明，MCNS患者尿液中检测到的阴离子白蛋白较少。大鼠肾内注入较少阴离子白蛋白后，大鼠肾小球基底膜负电荷减少，蛋白质排泄增加。根据这些结果推测，较少的阴离子白蛋白将中和GBM的负电荷，从而提高蛋白质的通透性。这将是蛋白质排泄的机制之一。较少