不同剂量酵母和腺嘌呤诱导大鼠痛风性肾病模型的建立比较  

Comparison of the establishment of rat model of gouty nephropathy induced by yeast and adenine

作　　者：蓝伦礼[1] 江滨[1] 刘梦楚 邹晓红[1] 曹骋[1] 曾元儿[1] 庞嘉颖 LAN Lun-li JIANG Bin LIU Meng-cha ZOU Xiao-hong CAO Chen ZENG Yuan-er Pang Jia-ying(Laboratory of Traditional Chinese Medicine Analysis, College of Traditional Chinese Medicine Guangzhou University of Chinese Medicine, Guangzhou 510006, China)

机构地区：[1]广州中医药大学中药学院中药分析实验室,广州510006

出　　处：《中国比较医学杂志》2017年第2期33-43,共11页Chinese Journal of Comparative Medicine

基　　金：南药研究协同创新中心专项基金(2011)

摘　　要：目的探讨不同剂量酵母、腺嘌呤和不同造模持续时间对大鼠痛风性肾病模型的影响。方法模型组雄性SD大鼠用15 g/kg酵母粉和50 mg/kg、100 mg/kg腺嘌呤分别灌胃,同时分别设置8、10、22、48的造模天数。比较各组肾脏肥大指数的大小,检测大鼠肾功能,尿液指标的变化,肾皮质β-N-乙酰氨基葡萄糖苷酶(NAG)含量,肝脏黄嘌呤氧化酶(XOD)活性的变化,同时观察大鼠肾脏病理改变。并用免疫组化技术检测肾脏组织NGAL、OAT1和TIMP-1的表达。结果随着模型组造模剂浓度的增加和造模时间的延长,肾脏病理改变越明显。100mg/kg腺嘌呤和15g/kg酵母共同造模8 d,与正常对照组比较,该组肾脏病理组织变化明显,炎性细胞浸润肾小管上皮细胞肿胀,肾小管和肾小球结构未被破坏;肾脏肥大指数较正常对照组增大(P<0.01);与正常对照组比较,模型A组,B组、E组、F组肾功能下降(P<0.01),模型A组、B组、E组、F组大鼠的24 h尿量,尿蛋白含量增多(P<0.01)。模型E组大鼠肾组织NGAL、TIMP-1的表达高于正常组大鼠(P<0.01),OAT1的表达低于正常组大鼠(P<0.01)。结论 100 mg/kg腺嘌呤和15 g/kg酵母共同造模8 d为较理想的造模剂量和造模持续时间,痛风性肾病模型大鼠肾损伤受蛋白NGAL、TIMP-1和OAT1的影响。Objective To explore the effect of yeast and adenine administration in different doses and different duration on the establishment of rat models of gouty nephropathy. Methods Fifty-seven healthy male 2 months old Dawley rats （220 -250 g） were used in this study. The rats of model groups were gavaged with 15 g/kg yeast and 50 mg/kg or 100 mg/kg adenine, for different number of days. The kidney hypertrophy index, kidney function, urine indexes, liver xanthine oxidase activity, N-acetyl-β-D-glucosaminidase （NAG） content in the renal cortex, and the renal histology were detected. The pathological changes of renal tissue were examined along with detection of the expression of NGAL, OAT1 and TIMP-1by immunohistochemical staining. Results The renal pathological changes were more obvious with the increasing yeast and adenine doses and time of modeling. Compared with the normal group, the renal histological changes in the group administered with 100 mg/kg adenine and 15 g/kg yeast for 8 days showed apparent inflammatory cell infiltration and swelling of tubular epithelial cells, but there was not destruction of renal tubules and glomerular structures, showing a significant difference between the model and normal groups （P 〈 0. 01 ）. Compared with that of the normal control group, kidney function was significantly decreased in the model groups A, B, E, and F （P 〈 0. 01）. Compared with the normal control group, the 24 h urine volume and content of urinary protein were significantly increased in the model groups A, B, E, and F （P 〈 0. 01 ） , and the expressions of protein OAT1 were significantly reduced in the renal tubules, while expressions of NGA, TIMP-1 were increased in the model group E （P 〈 0.01 ）. Conclusions Administration of adenine at a dose of 100 mg/kg and yeast at 15 g/kg for 8 days is an ideal procedure for the establishment of a rat model of gouty nephropathy. The renal alterations of this rat model of gouty nephropathy are affected by the changes of expressions of NGAL, TIMP-

关 键 词：痛风性肾病 酵母 腺嘌呤 肾功能 

分 类 号：R-33[医药卫生]