Tam F W, Smith J, Morel D, Karkar A M, Thompson E M, Cook H T, Pusey C D
Division of Medicine and Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Nephrol Dial Transplant. 1999 Jul;14(7):1658-66. doi: 10.1093/ndt/14.7.1658.
The aim of this study was to develop and characterize a rat model of crescentic glomerulonephritis which progresses to glomerulosclerosis and renal failure.
Glomerulonephritis was induced in Wistar Kyoto rats by a single injection of rabbit anti-glomerular basement membrane antiserum. Albuminuria and serum creatinine were monitored. Kidneys were examined, from 2.5 h to 44 days, using light-microscopy and immunohistochemistry. To characterize the glomerular inflammatory infiltrate, glomeruli were digested to single cells and analysed by fluorescence-activated cell sorter (FACS) and by immunohistochemistry on cytospins.
Rats developed albuminuria by 4 days and increased serum creatinine by day 18. Histology showed glomerular fibrinoid necrosis by day 4 and cellular crescents in a mean of 63% of glomeruli by day 11. By 6 weeks, rats had developed renal failure (mean creatinine >300 micromol/l) with 94% of the glomeruli showing glomerulosclerosis. The kidneys were also affected by severe interstitial nephritis and tubular loss. The glomeruli were infiltrated by monocytes/ macrophages (ED1+) and CD8+ (OX8+) cells. FACS analysis showed that CD8+ cells did not express T-cell markers (CD3, TCRalphabeta or TCRgammadelta) or the NK-cell marker (NKR-P1). FACS analysis of peripheral blood mononuclear cells demonstrated a population of monocytes reactive with OX8, and double-labelling of cytospin preparations of glomerular digests showed that a proportion of the CD8+ cells were a subset of ED1+ monocyte/macrophages.
We have characterized a reproducible model of crescentic glomerulonephritis which rapidly progresses to chronic renal failure with glomerulosclerosis and tubulo-interstitial scarring. This model will be useful for testing new therapeutic approaches in crescentic glomerulonephritis.
本研究的目的是建立并描述一种新月体性肾小球肾炎大鼠模型，该模型会进展为肾小球硬化和肾衰竭。
通过单次注射兔抗肾小球基底膜抗血清，在Wistar Kyoto大鼠中诱导肾小球肾炎。监测蛋白尿和血清肌酐。在2.5小时至44天期间，使用光学显微镜和免疫组织化学检查肾脏。为了描述肾小球炎性浸润的特征，将肾小球消化成单个细胞，并通过荧光激活细胞分选仪（FACS）以及对细胞涂片进行免疫组织化学分析。
大鼠在第4天出现蛋白尿，第18天血清肌酐升高。组织学显示，第4天出现肾小球纤维蛋白样坏死，第11天平均63%的肾小球出现细胞性新月体。到6周时，大鼠出现肾衰竭（平均肌酐>300微摩尔/升），94%的肾小球出现肾小球硬化。肾脏还受到严重间质性肾炎和肾小管丢失的影响。肾小球被单核细胞/巨噬细胞（ED1+）和CD8+（OX8+）细胞浸润。FACS分析显示，CD8+细胞不表达T细胞标志物（CD3、TCRαβ或TCRγδ）或NK细胞标志物（NKR-P1）。对外周血单个核细胞的FACS分析显示，存在一群与OX8反应的单核细胞，对肾小球消化物的细胞涂片制备进行双重标记显示，一部分CD8+细胞是ED1+单核细胞/巨噬细胞的一个亚群。
我们已经描述了一种可重复的新月体性肾小球肾炎模型，该模型迅速进展为伴有肾小球硬化和肾小管间质瘢痕形成的慢性肾衰竭。该模型将有助于测试新月体性肾小球肾炎的新治疗方法。
