Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota A
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Kidney Int. 1996 Jan;49(1):103-11. doi: 10.1038/ki.1996.14.
Glomerulosclerosis is characterized by progressive extracellular matrix accumulation and glomerular cell loss. The role of glomerular cell apoptosis in glomerulosclerosis was investigated in the rat remnant kidney model and in human glomerular diseases. We identified apoptotic cells in the glomeruli, tubules and interstitium in the remnant kidney by electron microscopy. DNA fragmentation, which is a biochemical characteristic of apoptosis, was detected by in situ nick end-labeling of fragmented DNA with terminal deoxynucleotidyl transferase and biotinylated deoxyuridine triphosphate. Fragmented DNA in the glomeruli and tubules increased with the progression of glomerulosclerosis in the remnant kidney model. This finding was also demonstrated in other glomerular sclerotic lesions such as IgA and lupus nephritis. The number of cells positive for nick end-labeling in the glomerulus significantly correlated with the degree of glomerulosclerosis and the deterioration of renal function. These results indicate that apoptosis is, at least in part, involved in the cell deletion of various glomerular diseases leading to sclerosis.
肾小球硬化的特征是细胞外基质进行性积聚和肾小球细胞丢失。在大鼠残余肾模型和人类肾小球疾病中研究了肾小球细胞凋亡在肾小球硬化中的作用。我们通过电子显微镜在残余肾的肾小球、肾小管和间质中鉴定出凋亡细胞。DNA片段化是凋亡的生化特征，通过用末端脱氧核苷酸转移酶和生物素化脱氧尿苷三磷酸对片段化DNA进行原位缺口末端标记来检测。在残余肾模型中，随着肾小球硬化的进展，肾小球和肾小管中的片段化DNA增加。这一发现也在其他肾小球硬化病变如IgA和狼疮性肾炎中得到证实。肾小球中缺口末端标记阳性的细胞数量与肾小球硬化程度和肾功能恶化显著相关。这些结果表明，凋亡至少部分参与了导致硬化的各种肾小球疾病的细胞缺失。
