Shimizu M, Shou I, Tsuge T, Abe M, Tomino Y
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nephron. 1998;79(1):67-72. doi: 10.1159/000044994.
Immunopathological studies were performed to determine whether the glomerular injuries in ddY mice, a model for IgA nephropathy (Berger's disease), are influenced by treatment with mizoribine, a new immunosuppressive agent. The ddY mice were treated with a low (0.05 mg/ml) or a high (0.1 mg/ml) dose of mizoribine for 35 weeks. Flow cytometry analysis showed that there was a marked decrease in the number of B cells and IgA-bearing B cells. In immunofluorescence, the deposition of IgA in the glomerular mesangial areas and capillary walls of the high-dose mizoribine-treated ddY mice was markedly decreased as compared with that of control ddY mice receiving drinking water. The glomerular mesangial expansion in the high-dose mizoribine-treated ddY mice was milder than that found in the control ddY mice. In 45-week-old ddY mice, the average number of intraglomerular cells in the high-dose and low-dose mizoribine-treated ddY mice was slightly lower than that in drinking water treated ddY mice. The levels of urinary protein excretion in the high-dose mizoribine-treated ddY mice were also lower than those in the low-dose mizoribine-treated or drinking water treated ddY mice. It appears that treatment of mizoribine might influence the proliferation of B cells, especially IgA-bearing B cells, and improve the glomerular IgA deposition and glomerular expansion in early-stage IgA nephropathy of ddY mice.
进行免疫病理学研究以确定米唑嘌呤（一种新型免疫抑制剂）治疗是否会影响ddY小鼠（IgA肾病（伯杰氏病）模型）的肾小球损伤。给ddY小鼠分别用低剂量（0.05mg/ml）或高剂量（0.1mg/ml）的米唑嘌呤治疗35周。流式细胞术分析显示B细胞和携带IgA的B细胞数量显著减少。在免疫荧光检查中，与饮用自来水的对照ddY小鼠相比，高剂量米唑嘌呤治疗的ddY小鼠肾小球系膜区和毛细血管壁中IgA的沉积明显减少。高剂量米唑嘌呤治疗的ddY小鼠肾小球系膜扩张程度比对照ddY小鼠轻。在45周龄的ddY小鼠中，高剂量和低剂量米唑嘌呤治疗的ddY小鼠肾小球内细胞的平均数量略低于饮用自来水治疗的ddY小鼠。高剂量米唑嘌呤治疗的ddY小鼠尿蛋白排泄水平也低于低剂量米唑嘌呤治疗或饮用自来水治疗的ddY小鼠。看来米唑嘌呤治疗可能会影响B细胞尤其是携带IgA的B细胞的增殖，并改善ddY小鼠早期IgA肾病中的肾小球IgA沉积和肾小球扩张。
