Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Nephron. 1998;79(2):206-14. doi: 10.1159/000045026.
Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Subsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4-6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.
在肾小球肾炎（GN）恢复模型中，受损肾小球可发生毛细血管修复。为了阐明毛细血管修复是否是GN后肾小球恢复的重要组成部分，我们研究了Thy-1 GN中修复性肾小球和节段性硬化瘢痕病变在炎性损伤后毛细血管修复的发展情况。通过给予抗Thy-1.1抗体在大鼠中诱导系膜溶解型肾小球损伤。到第3天，受损肾小球出现弥漫性系膜溶解和节段性微动脉瘤样扩张，内皮细胞数量减少。此后，在第5天至第3周出现组织学增殖性GN。内皮细胞增殖在第1天开始，在第5天达到峰值，肾小球内皮细胞数量增加，并在第7天超过对照值水平。到第7天，血管生成性肾小球毛细血管修复不仅通过毛细血管动脉瘤病变中残留内皮细胞的毛细血管再生过程发生，还通过源自肾小球血管极的新毛细血管生长过程发生。肾小球毛细血管腔的数量在第3周时也增加到对照水平。随后，系膜增生性GN消退，到第4 - 6周时，大多数肾小球通过毛细血管网络的重建恢复到正常结构。在肾小球毛细血管修复过程中，在第7天至第10天轻度内皮细胞增生期间，肾小球内皮细胞存在显著凋亡（凋亡内皮细胞/肾小球横截面积为0.06±0.02，而对照组为0.00±0.00，平均值±标准误；p<0.05）。在Thy-1 GN中，大多数受损肾小球通过血管生成性毛细血管修复而恢复。然而，10% - 30%的肾小球中仍存在节段性硬化瘢痕病变，肾小球毛细血管修复不完全。因此，可以得出结论，在GN中肾小球毛细血管网络破坏后，血管生成性毛细血管修复在受损肾小球的恢复中起重要作用，而不完全的毛细血管修复会导致受损肾小球出现硬化瘢痕病变。肾小球毛细血管修复通过残留内皮细胞的毛细血管再生以及肾小球血管极的新肾小球毛细血管生长过程发生。在肾小球毛细血管修复中，凋亡对于调节固有内皮细胞数量是必要的。
