Arai T, Morimoto K, Masaoka H, Kaneko O, Mera J, Kojima K, Nagase M, Kobayashi S, Ohtake T, Hishida A
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Nephrol Dial Transplant. 1997 Dec;12(12):2542-8. doi: 10.1093/ndt/12.12.2542.
Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria.
The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats.
Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups.
Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.
尽管众所周知，用眼镜蛇毒因子（CVF）治疗可预防被动型Heymann肾炎（PHN）大鼠的蛋白尿，但补体依赖性蛋白尿的确切机制尚未完全阐明。本研究的目的是从形态学上评估上皮下电子致密沉积物（EDD）的大小是否与蛋白尿的发生有关。
用钌红评估上皮下EDD的大小以及覆盖有上皮下EDD的外疏松层（LRE）中的阴离子位点，并在大鼠的PHN组和用CVF治疗的PHN组之间进行比较。
注射抗Fx1A后第3天和第4天出现明显蛋白尿。用CVF治疗PHN大鼠可预防蛋白尿（PHN + CVF组：n = 6）（第4天，53.6±38.8 vs 1.02±0.55 mg/天，P < 0.01）。在注射后第4天，在PHN大鼠的肾小球毛细血管壁上检测到大鼠C3，但在PHN + CVF大鼠中未检测到。两组均观察到上皮下EDD。定量形态计量分析显示，CVF治疗可减小上皮下EDD的大小以及肾小球上皮细胞的回缩程度。与没有上皮下EDD的LRE相比，两组中覆盖有EDD的LRE中的阴离子位点密度均降低。然而，两组之间未观察到差异。
血清补体的消耗可减少上皮下EDD以及EDD下方阴离子电荷减少的位点数量。因此，上皮下EDD的大小在蛋白尿的发生中起关键作用。
