Shibasaki T, Matsuda H, Gomi H, Usui M, Ishimoto F, Sakai O
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Am J Nephrol. 1996;16(2):167-72. doi: 10.1159/000168992.
Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B2 (TxB2) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB2 production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.
咪唑立宾（MZR）是一种嘌呤核苷抗生素，是一种有效的免疫抑制剂，可预防人类肾移植后的排斥反应。本研究旨在探讨MZR对给予嘌呤霉素氨基核苷（PAN）的大鼠产生的肾病的影响。与仅给予PAN的大鼠（PAN大鼠）相比，注射PAN和MZR的大鼠（PAN + MZR大鼠）的尿蛋白排泄量显著降低。尽管PAN + MZR大鼠在实验期间持续存在轻度低蛋白血症，但未观察到体重减轻或营养不良状态。给予MZR可逆转血清IgG和C3的降低。肾切片的聚乙烯胺（PEI）染色显示，与PAN大鼠相比，PAN + MZR大鼠的阴离子位点数量增加，这表明MZR改善了肾小球基底膜（GBM）的选择通透性。此外，与PAN大鼠相比，PAN + MZR大鼠的血栓素B2（TxB2）生成受到显著抑制。大剂量给予该药物后未观察到MZR的严重不良反应。PAN损伤的GBM电荷屏障的恢复或肾小球TxB2生成的减少可能是MZR给药诱导蛋白排泄减少的基础。
