Ougaard M K E, Kvist P H, Jensen H E, Hess C, Rune I, Søndergaard H
Department of Diabetes Complications Pharmacology, Novo Nordisk, Maaloev, Denmark.
Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Int J Nephrol. 2018 Mar 5;2018:8424502. doi: 10.1155/2018/8424502. eCollection 2018.
Using the nonaccelerated murine nephrotoxic nephritis (NTN) as a model of chronic kidney disease (CKD) could provide an easily inducible model that enables a rapid test of treatments. Originally, the NTN model was developed as an acute model of glomerulonephritis, but in this study we evaluate the model as a CKD model and compare CD1 and C57BL/6 female and male mice. CD1 mice have previously showed an increased susceptibility to CKD in other CKD models. NTN was induced by injecting nephrotoxic serum (NTS) and evaluated by CKD parameters including albuminuria, glomerular filtration rate (GFR), mesangial expansion, and renal fibrosis. Both strains showed significant albuminuria on days 2-3 which remained significant until the last time point on days 36-37 supporting dysfunctional filtration also observed by a significantly declined GFR on days 5-6, 15-17, and 34-37. Both strains showed early progressive mesangial expansion and significant renal fibrosis within three weeks suggesting CKD development. CD1 and C57BL/6 females showed a similar disease progression, but female mice seemed more susceptible to NTS compared to male mice. The presence of albuminuria, GFR decline, mesangial expansion, and fibrosis showed that the NTN model is a relevant CKD model both in C57BL/6 and in CD1 mice.
使用非加速型小鼠肾毒性肾炎（NTN）作为慢性肾脏病（CKD）模型，可以提供一个易于诱导的模型，便于快速测试各种治疗方法。最初，NTN模型是作为肾小球肾炎的急性模型开发的，但在本研究中，我们将该模型评估为CKD模型，并比较了CD1和C57BL/6品系的雌性和雄性小鼠。在其他CKD模型中，CD1小鼠先前已显示出对CKD的易感性增加。通过注射肾毒性血清（NTS）诱导NTN，并通过包括蛋白尿、肾小球滤过率（GFR）、系膜扩张和肾纤维化在内的CKD参数进行评估。两个品系在第2 - 3天均出现显著蛋白尿，直至第36 - 37天的最后一个时间点仍保持显著，这也支持了在第5 - 6天、15 - 17天和34 - 37天观察到的GFR显著下降所表明的滤过功能障碍。两个品系在三周内均出现早期进行性系膜扩张和显著肾纤维化，提示CKD的发展。CD1和C57BL/6雌性小鼠表现出相似的疾病进展，但与雄性小鼠相比，雌性小鼠似乎对NTS更敏感。蛋白尿、GFR下降、系膜扩张和纤维化的存在表明，NTN模型在C57BL/6和CD1小鼠中都是一种相关的CKD模型。
