Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.
Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.
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DOI：
10.1093/ndt/gfh302
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发表时间：
2004-09
期刊：
影响因子：
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通讯作者：
Shin-ichi Takeda;Masafumi Takahashi;Y. Sado;K. Takeuchi;Y. Hakamata;H. Shimizu;Takashi Kaneko;Hisashi Yamamoto;C. Ito;S. Ookawara;Y. Asano;E. Kusano;E. Kobayashi
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文献类型：
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作者：
Shin-ichi Takeda;Masafumi Takahashi;Y. Sado;K. Takeuchi;Y. Hakamata;H. Shimizu;Takashi Kaneko;Hisashi Yamamoto;C. Ito;S. Ookawara;Y. Asano;E. Kusano;E. Kobayashi
肾小球新月体形成是肾小球肾炎（GN）侵袭性形式的一个显著特征，与预后不良相关。我们研究了有效的免疫抑制剂霉酚酸酯（MMF）是否可以防止大鼠抗肾小球基底膜（GBM）GN模型中新月体的形成。方法向雌性Wistar-Kyoto（WKY/NCrj）大鼠注射抗GBM抗体诱导GN伴肾小球新月体。实验大鼠分为两组：大鼠经口给予溶剂（0.5%羧甲基纤维素）或MMF（20 mg/kg/天）。测量体重并评价尿液和血液样本。第14天处死大鼠，进行组织学分析。用逆转录-聚合酶链反应（RT-PCR）检测肾组织细胞因子和粘附分子的mRNA表达。结果造模后大鼠出现明显的蛋白尿、肾小球新月体形成和肾小球硬化，经霉酚酸酯治疗后，上述指标明显降低。还观察到明显的肾小球巨噬细胞和T细胞浸润，MMF处理可显着抑制巨噬细胞，但不能抑制T细胞浸润。RT-PCR和免疫组化分析显示，骨桥蛋白的mRNA和蛋白的表达减少，与治疗的霉酚酸酯。此外，在肾小球肾炎早期给予霉酚酸酯治疗可抑制蛋白尿、肾小球新月体形成和肾小球硬化。结论：这些结果表明，霉酚酸酯在抑制肾小球新月体形成的GN的治疗潜力，并提供了新的见解，通过霉酚酸酯治疗新月体GN的改善机制。
BACKGROUND Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat. METHODS GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis. CONCLUSIONS These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.