New rat model induced by anti-glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end-stage renal failure
New rat model induced by anti-glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end-stage renal failure
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DOI：
10.1111/j.1440-1827.2008.02237.x
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发表时间：
2008-06-01
影响因子：
2.2
通讯作者：
Yamada, Yoshihisa
中科院分区：
文献类型：
--
作者：
Nakano, Yoshimasa;Hirano, Takahiro;Yamada, Yoshihisa
本研究的目的是建立一种新的抗肾小球基底膜肾炎模型，该模型在单次给药兔抗大鼠肾小球基底膜抗体仅4周后血浆肌酐水平显著升高。根据肾脏形态学，在疾病诱导后第7天早期观察到肾小球病变，表现为系膜扩张和肾小球簇与鲍曼囊粘连；注射抗体14天后，约90%的肾小球出现粘连。21天后，大鼠表现出明显的肾小球硬化/透明质变和以间质纤维化为特征的严重小管间质病变。对肾炎大鼠尿足细胞的排泄进行了研究，发现尿足细胞的丢失可能与肾损伤的进展密切相关。由于这个新模型简单且可重复地证明了终末期肾脏疾病的发展，它将有助于阐明慢性肾损伤不可逆进展的机制，以及开发慢性肾功能衰竭的治疗药物。
The aim of the present study was to introduce a new anti-glomerular basement membrane nephritis model in which plasma creatinine levels dramatically increased only 4 weeks after a single administration of rabbit antirat glomerular basement membrane antibody in Sprague-Dawley rats. According to renal morphology, glomerular lesions characterized by mesangial expansion and adhesion of the glomerular tuft to Bowman's capsule were observed in the early stage at day 7 after disease induction; adhesion was detected in approximately 90% of glomeruli 14 days after antibody injection. After 21 days the rats exhibited pronounced glomerulosclerosis/hyalinosis and severe tubulointerstitial lesions characterized by interstitial fibrosis. Urinary podocytes excreted in nephritis rats were studied and it was found that urinary podocyte loss might be closely related to progression of renal injury. Because this new model simply and reproducibly demonstrates development of end-stage renal disease, it will be beneficial for elucidating mechanisms by which chronic renal injury irreversibly progresses, as well as for developing therapeutic agents for chronic renal failure.