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Research on The Mechanisms of Tubulointerstitial Injury by Proteinuria.

蛋白尿损伤肾小管间质的机制研究。

基本信息

批准号：
09671160
负责人：
MATSUO Seiichi
金额：
$ 2.11万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The aim of this project was to investigate the mechanisms of tubulointerstitial injury associated with proteinuria, since tubulointerstitial injury and proteinuria are closely related with each other and both of them are the better predictors for prognosis of renal injury. In the present study, the role of complement present in the tubular fluid of nephrotic subjects was investigated. In the first part of experiment using rats made nephrotic by aminonucleoside in which significant tubulointerstitial injury and tubular deposition of complement were observed at 7 days, the following results were obtained. (1) Depletion of serum complement by cobra venom factor (CVF) did not affect proteinuria, but significantly reduced deposition of complement in the tubules and tubulointerstitial injury, (2) soluble CR1, an inhibitor of complement activation at C3 level, had the same effects as CVF.In the second part, complement activation products (CAP, i.e., iC3b and Bb at C3 level, and MAC at C9 level) were measured in the patients with various glomerular diseases. The results *otained were as follow ; (1) Urinary excretion of CAP was positively correlated with the amount of proteinuria, (2) among proteinuric patients, those with focal glomerular sclerosis and diabetic nephropathy showed significantly elevated amount of CAP in the urine, (3) in case of membranous nephropathy, urinary excretion of MAC was increased, whereas iC3b and Bb were not increased, (4) in the patients with renal insufficiency, correction of acidosis by sodium bicarbonate significantly reduced urinary excretion of CAP without affecting the serum level of CAP and urinary protein excretion. These results indicate that, in the proteinuric condition, complement components present in the urine are activated in the tubular lumen and injure the tubular cells resulting in the promotion of tubulointerstitial injury.

由于肾小管间质损伤与蛋白尿密切相关，两者均是肾损伤预后的较好预测指标，因此本课题旨在探讨肾小管间质损伤与蛋白尿相关的机制。在本研究中，补体存在于肾病患者的肾小管液中的作用进行了研究。在实验的第一部分中，使用由氨基胍制成的肾病大鼠，其中在第7天观察到显著的肾小管间质损伤和补体的肾小管沉积，获得了以下结果。(1)CVF对血清补体的消耗不影响蛋白尿，但能显著减少补体在肾小管的沉积和肾小管间质的损伤。（2）可溶性补体受体1（C3水平的补体激活抑制剂）具有与CVF相同的作用。在各种肾小球疾病患者中测量了C3水平的iC 3b和Bb，以及C9水平的MAC。所得结果如下：（1）尿CAP排泄量与尿蛋白量呈正相关;（2）在蛋白尿患者中，局灶性肾小球硬化和糖尿病肾病患者尿CAP显著升高;（3）膜性肾病患者尿MAC排泄量增加，而iC 3b和Bb无增加。（4）在肾功能不全患者中，碳酸氢钠纠正酸中毒可显著减少尿CAP排泄，而不影响血清CAP水平和尿蛋白排泄。这些结果表明，在蛋白尿条件下，存在于尿中的补体成分在肾小管腔中被激活并损伤肾小管细胞，导致肾小管间质损伤的促进。