PATHOGENESIS OF MEMBRANOUS GLOMERULONEPHROPATHY

这项研究计划的目的是为了更多地了解 大鼠自身免疫复合体肾病(AIC)及其发病机制的研究 人类特发性膜性肾小球肾病(MGN)具体地说，就是： 1)我们将检验一个假设，即一种动物的易感性 AIC的发生或人的MGN的发生与a排泄有关 该物种或个体尿液中的刷状边界抗原(BBAg)，2) BBAg放射免疫检测方法的建立及深入研究 AIC的发病机制：3)确定BBAg在AIC中的超微结构定位 肾脏，4)确定BBAg是否由培养的近端肾小管产生， 5)研究人工制造的物理屏障在 口服银致肾小球基底膜损伤 硝酸盐对免疫复合体在上皮下层定位的影响 外源性抗原过量作为治疗手法的效果研究 在AIC的进程中。这些方法将包括免疫荧光、辣根 过氧化物酶标记BBAg的特异性抗体和电子显微镜， 近端肾小管细胞的培养、放射免疫分析及柱层析 从这些实验中收集的数据将：1)增强 大鼠AIC发病机制及MGN发病机制的认识 人类，2)可以提供方法来识别易患此病的个体 MGN，3)可能导致治疗AIC的方法，并可能导致MGN和4)产生 关于物理屏障在免疫复合体沉积中的作用的信息 在肾小球肾炎中。

The objective of this research proposal is to understand more about the pathogeneses of the autologous immune-complex nephropathy of rats (AIC) and of the idiopathic membranous glomerulonephropathy (MGN) in humans. Specifically: 1) we will test the hypothesis that the susceptibility of a species of an animal to develop AIC or of a human to develop MGN is related to the excretion of a brush border antigen (BBAg) in the urine of that species or the individual, 2) develop a more specific radioimmunoassay for measuring BBAg and study in depth the pathogenesis of AIC, 3) determine the ultrastructural location of BBAg in kidney, 4) determine if BBAg is produced by the cultured proximal renal tubules, 5) study the effect of an artifically produced physical-barrier in the glomerular basement membrane induced by the oral administration of silver nitrate on the immune-complex localization in the subepithelial position and 6) study the effect of exogenously given antigen excess as a therapeutic maneuver on the course of AIC. The methods will include immunofluorescence, horseradish peroxidase labelled specific antibodies to BBAg and electron microscopy, culturing of proximal renal tubular cells, radioimmunoassay and column chromatography, etc. Data collected from these experiments will: 1) enhance our knowledge about the pathogenesis of AIC of rats and possibly of MGN in humans, 2) may provide methods to identify individuals susceptible to develop MGN, 3) may lead to methods to treat AIC and possibly MGN and 4) produce information on the role of a physical barrier on the immune-complex deposition in glomerulonephritis.