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裴忆雪,刘永杰,张笛,刘德俊,徐凌云.建立高尿酸血症性肾损害小鼠模型的实验研究[J].中国比较医学杂志,2018,28(9):46~54.
建立高尿酸血症性肾损害小鼠模型的实验研究
Establishment of a hyperuricemia mouse model with renal damage
投稿时间:2018-03-30  
DOI:10.3969/j. issn. 1671 -7856. 2018. 09. 008
中文关键词:  高尿酸血症  肾损害  动物模型  小鼠
英文关键词:hyperuricemia  renal injury  animal modeling  mouse
基金项目:
作者单位E-mail
裴忆雪 武汉轻工大学生物与制药工程学院,武汉 430023 172109078@ qq. com 
刘永杰 武汉轻工大学生物与制药工程学院,武汉 430024  
张笛 武汉轻工大学生物与制药工程学院,武汉 430025  
刘德俊 武汉轻工大学生物与制药工程学院,武汉 430026  
徐凌云 武汉轻工大学生物与制药工程学院,武汉 430027 doctorxly9898@163. com 
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中文摘要:
      目的 建立合理?稳定的高尿酸血症肾损害小鼠模型,为筛选及研究治疗高尿酸血症肾病的药物提供病理模型?方法 将氧嗪酸钾?次黄嘌呤?腺嘌呤?乙胺丁醇和酵母膏5 种造模剂单用?两药合用或三药联用,观察不同造模时间?造模剂量和造模方式所建立的小鼠高尿酸血症肾损害模型的血清尿酸?尿素氮以及肌酐水平?肝脏黄嘌呤氧化酶(xanthine oxidase,XOD)和腺苷脱氨酶(adenosine deaminase,ADA)活性的变化?肾脏的病理学改变以及各组体重变化情况?结果 与正常组比较,次黄嘌呤和氧嗪酸钾联用单次造模组小鼠血清尿酸水平及尿素氮明显升高( P < 0. 01),肾皮质可见肾小管管型,肾髓质可见盐类结晶;次黄嘌呤?乙胺丁醇和氧嗪酸钾三药联用7 d组小鼠血清尿酸水平及尿素氮明显升高( P < 0. 01),肝脏XOD 活性明显降低( P < 0. 05),肾近曲小管内可见嗜酸性不溶性蛋白;酵母膏和氧嗪酸钾联用14 d 组以及酵母膏?腺嘌呤和氧嗪酸钾联用14 d 组,与正常组相比,小鼠血清尿酸?尿素氮以及肌酐值均显著升高( P < 0. 01),酵母膏和氧嗪酸钾联用组可见肾小管上皮细胞脱落,肾近曲小管内可见嗜酸性不溶性蛋白,酵母膏?腺嘌呤和氧嗪酸钾联用组小鼠肾髓质可见盐类结晶?酵母膏和氧嗪酸钾联用组比酵母膏?腺嘌呤和氧嗪酸钾联用组小鼠体重增长更快,两组差异有显著性( P < 0. 05)?结论 与其他造模方式比较,由于酵母膏和氧嗪酸钾联用所建立的高尿酸血症肾损害小鼠模型更加稳定,对小鼠体重无明显影响,同时该造模方式更符合临床特点,因此采用酵母膏和氧嗪酸钾联用14 d 建立高尿酸血症肾损害小鼠模型更为合适?
英文摘要:
      Objective To provide a pathological model for the screening and study of drugs for the treatment of hyperuricemic nephropathy by establishing a reasonable and stable mouse model with hyperuricemic kidney injury. Methods By administering one, two, or three of five drugs, oteracil potassium, hypoxanthine, adenine, ethambutol, and yeast extract, a model was established with hyperuricemia renal injury in KM mice, at different modeling times by using different modeling doses and modeling methods. The changes in serum uric acid, urea nitrogen, creatinine, liver xanthine oxidase (XOD), and adenosine deaminase (ADA) activity were determined, and the variations in weight of each group were analyzed. Results Compared with the normal group, the serum uric acid level and urea nitrogen level in the mice significantly increased ( P < 0. 01) in the group with 1?day combination medication of hypoxanthine and oteracil potassium, the renal tubular type was abundantly observed in renal cortex, and salt crystals were abundantly observed in renal medulla. The serum uric acid level and urea nitrogen level in the mice increased significantly ( P < 0. 01), and liver XOD activity decreased ( P < 0. 05) in the group with 7?day combination medication of hypoxanthine, ethambutol, and oteracil potassium, and eosinophilic insoluble proteins were found in some of the proximal tubules of the renal cortex. The serum uric acid level, urea nitrogen level, and creatinine level in the mice significantly increased ( P < 0. 01) in the group with 14?day combined medication of yeast extract and oteracil potassium and the group with 14?day combined medication of yeast extract, adenine, and oteracil potassium. Renal tubular epithelial cells fell off in the renal cortex, and eosinophilic insoluble proteins were visible in some of the proximal tubules of the mice in the group with combined medication of yeast extract and oteracil potassium. Salt crystals were abundantly observed in the renal medulla of the mice in the group with combined medication of yeast extract, adenine, and oteracil potassium. The body weight of the yeast extract and oteracil potassium group increased faster than that of the yeast extract, adenine, and oteracil potassium group, with a significant difference between their body weights ( P < 0. 05). Conclusions Compared with other modeling method , the mouse model with hyperuricemic renal damage induced by the combined medication of yeast extract and oteracil potassium was more stable and its establishment had no significant effect on the body weight of the mice. Therefore, it is more suitable to use yeast extract combined with oteracil potassium once a day for 14 days to establish a mouse model of hyperuricemia renal damage.
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