Yo Yoshikage, Braun Michael C, Barisoni Laura, Mobaraki Hideko, Lu Huiyan, Shrivastav Shashi, Owens Jennie, Kopp Jeffrey B
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-1268, USA.
Nephron Exp Nephrol. 2003;93(3):e92-106. doi: 10.1159/000069551.
In order to develop a model in mouse similar to anti- Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation.
为了在小鼠中建立一种类似于大鼠抗Thy-1肾炎的模型，我们制备了针对SV40转化的小鼠系膜（MES 13）细胞的绵羊抗血清。在体内，经抗小鼠系膜细胞血清处理的小鼠出现严重氮质血症，在第6天达到峰值，蛋白尿在第8天达到峰值，呈剂量依赖性。光学显微镜和电子显微镜检查显示肾小球基底膜重复、系膜溶解、内皮下和系膜电子致密沉积物以及足突消失。在第4天，肾小球毛细血管丛细胞数量显著减少，在第2天和第4天凋亡细胞数量增加。SCID小鼠和缺乏C3的小鼠对抗小鼠系膜细胞血清表现出相似的反应，表明在该模型中，T细胞、B细胞和补体不是肾小球损伤所必需的。在体外，经抗小鼠系膜细胞血清处理的系膜细胞显示乳酸脱氢酶释放增加、细胞存活率降低和凋亡细胞死亡增加。抗小鼠系膜细胞血清诱导以系膜溶解和系膜细胞凋亡为特征，随后伴有细胞增殖的肾小球病。
