Cheng Q L, Orikasa M, Morioka T, Kawachi H, Chen X M, Oite T, Shimizu F
Department of Immunology, Niigata University School of Medicine, Japan.
Clin Exp Immunol. 1995 Oct;102(1):181-5. doi: 10.1111/j.1365-2249.1995.tb06653.x.
A new animal model of progressive glomerulosclerosis was developed by administering a single i.v., injection of MoAb 1-22-3 to unilaterally nephrectomized rats. Renal morphological analysis revealed that glomerular lesions characterized by mesangial cell proliferation and mesangial matrix expansion were induced in about 95% of the glomeruli. Approximately 20% of the glomeruli of the unilaterally nephrectomized rats showed sclerosis or segmental sclerosis by week 6 after MoAb injection and crescent formation was observed in some glomeruli (ca 4%). Cellular infiltration was also noted in some parts of the interstitium. Increased expression of transforming growth factor-beta (TGF-beta) was observed in the unilaterally nephrectomized rats treated with MoAb 1-22-3, but we could not demonstrate pathological involvement of platelet-derived growth factor (PDGF), even though early-stage mesangial cell proliferation was observed. The mechanism of mesangial cell proliferation in this model remains to be elucidated. The relatively short period of time needed to induce the sclerotic changes in considered to be a great advantage of this model for clarifying the mechanisms involved in the chronic progression of mesangial proliferative glomerulonephritis.
通过对单侧肾切除的大鼠静脉内单次注射单克隆抗体1-22-3,建立了一种新的进行性肾小球硬化动物模型。肾脏形态学分析显示,约95%的肾小球出现了以系膜细胞增殖和系膜基质扩张为特征的肾小球病变。在注射单克隆抗体后第6周,单侧肾切除大鼠约20%的肾小球出现硬化或节段性硬化,部分肾小球(约4%)观察到新月体形成。间质的某些部位也有细胞浸润。在用单克隆抗体1-22-3处理的单侧肾切除大鼠中,观察到转化生长因子-β(TGF-β)表达增加,尽管观察到早期系膜细胞增殖,但我们未能证实血小板衍生生长因子(PDGF)的病理参与。该模型中系膜细胞增殖的机制仍有待阐明。诱导硬化性改变所需的时间相对较短,被认为是该模型在阐明系膜增生性肾小球肾炎慢性进展所涉及机制方面的一大优势。