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  • 蒋茜,郭永平,王毅兴,等.高尿酸血症肾损害大鼠模型的建立[J].同济大学学报(医学版),2012,33(1):27-31.    [点击复制]
  • JIANG Qian,GUO Yong-ping,WANG Yi-xing,et al.Establishment of hyperuricemia rat model with renal damage[J].同济大学学报(医学版),2012,33(1):27-31.   [点击复制]
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高尿酸血症肾损害大鼠模型的建立
蒋茜1,郭永平1,王毅兴1,高建东2,严海东1
0
(1. 同济大学附属东方医院肾内科,上海,200120;2. 上海市浦东医院肾内科,上海,200120)
摘要:
目的考察3种不同的造模方法,以建立高尿酸血症肾损害大鼠模型,确定建立高尿酸血症肾损害大鼠模型的有效实验方法。方法选用清洁级雄性SD大鼠24只,体质量(200±20)g,随机分为正常组、模型Ⅰ组、模型Ⅱ组、模型Ⅲ组,每组6只。正常组实验过程中正常饲养,模型Ⅰ组根据大鼠体质量以腺嘌呤(0.1 g/kg·d-1)与氧嗪酸钾(1.5g/kg·d-1)混悬液灌胃给药;模型Ⅱ组根据大鼠体质量以腺嘌呤(0.15 g/kg·d-1)与氧嗪酸钾(0.6g/kg·d-1)的混悬液,每日腹腔注射两次;模型Ⅲ组大鼠以腺嘌呤(20mg/d)和乙胺丁醇(50mg/d)的混悬液灌胃给药。连续给药28 d,检测第7天、第14天、第21天、第28天各组大鼠的血清尿酸(serum uric acid,SUA)、肌酐(creatinine,CRE)、尿素氮(urea nitrogen,BUN),28 d后留取大鼠肾脏标本行H-E及MASSON染色,观察肾脏病理变化情况。结果模型Ⅰ组大鼠第7天、第14天、第21天及第28天的血尿酸较正常组升高(P<0.05),血肌酐、尿素氮在第14天、第21天及第28天较正常组均升高(P<0.05);模型Ⅱ组大鼠仅第14天及第28天的血尿酸值较正常组有所升高(P<0.05),其血肌酐、尿素氮在第7天、第14天、第21天及第28天较正常组升高(P<0.05);模型Ⅲ组大鼠仅第7 d的血尿酸值较正常组升高(P<0.05),其余时间点无明显差异,其血肌酐在第7天、第14天、第21天及第28天较正常组升高(P<0.01),血尿素氮在第14天、第21天及第28天较正常组升高(P<0.01);肾组织病理结果提示各模型组可见明显肾小管和间质损伤,其中模型Ⅲ组肾脏组织结构存在广泛性损害。结论腺嘌呤和氧嗪酸钾联合灌胃的造模方法可以成功地制备出尿酸稳定升高、类似于人类尿酸性肾病的高尿酸血症肾损害大鼠模型。
关键词:  高尿酸血症肾损害  大鼠模型  尿酸酶抑制剂
DOI:10.3969/j.issn1008-0392.2012.01.006
基金项目:
Establishment of hyperuricemia rat model with renal damage
JIANG Qian1,GUO Yong-ping1,WANG Yi-xing1,GAO Jian-dong2,YAN Hai-dong1
(1.Dept.of,East Hospital,Tongji University,Shanghai 200120,China;2.Dept.of,Shanghai Pudong Hospital,Shanghai 200120,China)
Abstract:
Objective To establish rat model of hyperuricemia with renal damage.Methods Twenty four SD rats were divided into 4 groups with 6 in each.Rats in modelⅠgroup were given with adenine at the dosage of 0.1g/(kg·d)-1 and potassium oxonate at the dosage of 1.5g/(kg·d)-1 by gavage;rats in modelⅡgroup were given with adenine at the dosage of 0.15g/(kg·d)-1 and potassium oxonate at the dosage of 0.6 g/(kg ? d)-1by intraperitoneal injection;rats in modelⅢgroup were given with adenine(20 mg/d) and ethambutolal(50 mg/d) by gavage;rats in control group were given normal diet.The drug administration lasted for 28 days.The serum uric acid (SUA),creatinine(CRE),urea nitrogen(BUN) were measured on the day of 7th,14th,21th and 28th.The pathological changes of renal tissue in rats were examined after 28 days.Results Compared with the normal group,the serum uric acid in modelⅠgroup increased(P<0.05) on the day of 7th,14th,21th and 28th;the creatinine,urea nitrogen increased on the day of 14th,21th and 28th(P<0.05).The serum uric acid in modelⅡgroup decreased(P<0.05) on the day of 14th and 28th;the creatinine,urea nitrogen increased on the day of 7th,14th,21th and 28th(P<0.05).The serum uric acid in modelⅢgroup increased on the day of 7 th(P<0.05);the creatinine had increased (P<0.01) on the day of 7th,14th,21th and 28th;and the urea nitrogen of also increased(P<0.01) on the day of 14th,21th and 28th.Pathological examination on renal tissue revealed that the tubular and interstitial injury in all 3 model groups;and there was extensive damage of renal tissue in modelⅢgroup.Conclusion The rat model of hyperuricemia with renal damage has been successfully established by stomach irrigation with adenine and potassium oxonate.
Key words:  hyperuricemia with renal damage  rat model  potassium oxonate

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