Claramunt Débora, Gil-Peña Helena, Fuente Rocío, García-López Enrique, Loredo Vanessa, Hernández-Frías Olaya, Ordoñez Flor A, Rodríguez-Suárez Julián, Santos Fernando
Universidad de Oviedo, Asturias, Spain; and.
Hospital Universitario Central de Asturias, Oviedo, Spain.
Am J Physiol Renal Physiol. 2015 Jul 1;309(1):F57-62. doi: 10.1152/ajprenal.00051.2015. Epub 2015 May 13.
Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 μm/day, control rats: 293 ± 16 μm/day, and PF rats: 251 ± 10 μm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 μm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.
生长发育迟缓是儿科慢性肾脏病（CKD）的主要表现。在临床研究中，很难评估各种致病因素的参与情况。在此，我们提出一种腺嘌呤诱导的CKD实验模型，用于研究生长发育障碍。研究了三组（每组n = 10）断奶雌性大鼠：正常饮食（对照组）、0.5%腺嘌呤饮食（AD组）和与AD组配对喂养的正常饮食组（PF组）。21天后，分析血清尿素氮、肌酐、甲状旁腺激素（PTH）、体重和体长增加、作为纵向生长速率指标的股骨骨前沿进展、生长板组织形态计量学、软骨细胞增殖活性、骨结构、主动脉钙化和肾脏组织学。结果为平均值±标准误。AD组大鼠出现肾衰竭（血清尿素氮：70±6mg/dl，肌酐：0.6±0.1mg/dl）和继发性甲状旁腺功能亢进（PTH：480±31pg/ml）。AD组大鼠体重（AD组大鼠：63.3±4.8g，对照组大鼠：112.6±4.7g，PF组大鼠：60.0±3.8g）和体长（AD组大鼠：7.2±0.2cm，对照组大鼠：11.1±0.3cm，PF组大鼠：8.1±0.3cm）增加较低，骨前沿进展也较低（AD组大鼠：141±13μm/天，对照组大鼠：293±16μm/天，PF组大鼠：251±10μm/天），表明生长发育迟缓。AD组大鼠软骨细胞成熟和增殖过程受损，生长板终末软骨细胞高度较低（对照组和PF组大鼠分别为26.2±1.9和23.9±1.3μm，AD组大鼠为21.7±2.3μm），增殖活性指数也较低（AD组大鼠：30±2%，对照组大鼠：38±2%，PF组大鼠：42±3%）。AD组大鼠骨初级松质骨结构明显紊乱。总之，幼鼠腺嘌呤诱导的CKD与生长发育迟缓及软骨内成骨紊乱有关。该动物实验方案可能是研究CKD生长发育的一种有用的新实验模型。
