Kanno K, Okumura F, Toriumi W, Ishiyama N, Nishiyama S, Naito K
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
Jpn J Pharmacol. 1998 Jun;77(2):129-35. doi: 10.1254/jjp.77.129.
We investigated nephrotoxic serum (NTS)-induced glomerulonephritis in Wistar-Kyoto (WKY) rats as a model to evaluate antinephritic agents. WKY rats required only a small amount of NTS to induce crescentic glomerulonephritis and the rats progressively lost their renal function in a few weeks. In a comparative study with WKY and Sprague-Dawley (SD) rats, WKY rats showed a normal distribution pattern in the severity of proteinuria with a small variance. While SD rats needed a much higher amount of NTS to exhibit a comparable proteinuria which was not normal and had a large variance. The effects of clinically available antinephritic drugs, methylprednisolone, cyclophosphamide and cyclosporin A, were studied in both strains. In WKY rats, these drugs significantly inhibited the proteinuria, glomerular histological changes and decrease in creatinine clearance. On the other hand, such significant inhibitory effects on proteinuria were not observed with any of these drugs in SD rats. In conclusion, NTS nephritis in WKY rats may prove to be a useful model for studying antinephritic agents.
我们研究了用肾毒性血清（NTS）诱导Wistar-Kyoto（WKY）大鼠患肾小球肾炎，以此作为评估抗肾炎药物的模型。WKY大鼠只需少量NTS就能诱发新月体性肾小球肾炎，且大鼠在几周内肾功能逐渐丧失。在一项对WKY大鼠和Sprague-Dawley（SD）大鼠的比较研究中，WKY大鼠蛋白尿严重程度呈正态分布模式，方差较小。而SD大鼠需要大量NTS才能出现类似的蛋白尿，且这种蛋白尿不正常，方差较大。我们研究了两种品系中临床可用的抗肾炎药物甲泼尼龙、环磷酰胺和环孢素A的效果。在WKY大鼠中，这些药物显著抑制了蛋白尿、肾小球组织学变化以及肌酐清除率的降低。另一方面，在SD大鼠中，这些药物均未观察到对蛋白尿有如此显著的抑制作用。总之，WKY大鼠的NTS肾炎可能是研究抗肾炎药物的有用模型。
