建立痛风性肾病并发慢性肾功能衰竭动物模型方法的探讨

作者	单位
邢儒伶	青岛大学医学院第二附属医院
任伟	青岛市中心医院中医科青岛大学医学院附属医院山东省代谢性疾病重点实验室青岛市常见病重点实验室痛风病实验室
孟冬梅	青岛市中心医院中医科青岛大学医学院附属医院山东省代谢性疾病重点实验室青岛市常见病重点实验室痛风病实验室
李长贵	青岛市中心医院中医科青岛大学医学院附属医院山东省代谢性疾病重点实验室青岛市常见病重点实验室痛风病实验室

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中文摘要:

目的探讨痛风性肾病并发慢性肾功能衰竭(简称慢肾衰)动物模型的建立方法。方法以10%高酵母饲料喂养6～8周龄雄性Wistar大鼠,分别以100、150、200、250、300mg/(kg.d)腺嘌呤灌胃,动态监测大鼠血清尿素氮(BUN)、肌酐(Cr)及血尿酸(UA)水平的变化,同时观察大鼠肾脏病理改变。结果与正常对照组比较,以100mg/(kg.d)腺嘌呤灌胃7天,大鼠血清BUN、Cr及血UA均明显升高(P<0.05),同时肾脏病理组织学出现痛风性肾病的病理改变,随着造模时间的延长,上述生化指标及肾脏病理组织学变化更明显,在第26天(约4周)血Cr达到慢肾衰水平,而41天(约第6周)血Cr明显超过慢肾衰水平。血UA于造模后第7天达到较高水平,较长时间内维持在高水平上,血UA在第41～48天之间迅速下降,肾脏病理组织学淋巴细胞浸润,纤维组织增生加重,造模48天时在上述病变基础上纤维组织增生明显,间质纤维化。而其他剂量腺嘌呤灌胃至14天,与正常对照组比较,血清BUN、Cr及血UA均明显升高(P<0.05),达到肾功能衰竭水平;恢复正常饲料喂养,17天后血清BUN、Cr及血UA水平明显下降,至35天时,上述指标恢复接近正常水平。结论用10%高酵母饲料喂养雄性Wistar大鼠,同时予以100mg/(kg.d)体重腺嘌呤灌胃5周,可建立理想的痛风性肾病并发慢肾衰的实验动物模型。

英文摘要:

Objective To explore the method for establishing animal models of gouty nephropathy complicated with chronic renal failure.Methods Six-eight weeks old male Wistar rats were fed with 10% fodder yeast.The adenine at the daily dose of 100,150,200,250,and 300 mg/kg was administrated to them by gastrogavage.The serum levels of blood urea nitrogen(BUN),creatinine(Cr),and uric acid(UA) were dynamically monitored.Meanwhile,the pathological changes of rat kidney were observed.Results Compared with the normal control group,serum BUN,Cr,and UA obviously increased in rats administered with 100 mg/kg for 7 days(P<0.05).Meanwhile,pathological changes as gouty nephropathy occurred.Along with the prolongation of the modeling time,the aforesaid biochemical indices and pathohistological changes of the kidney were more obvious.The blood Cr level just reached the chronic renal failure level on the 26th day of the administration(about the 4th week),and obviously exceeded the renal failure level on the 41st day(about the 6th week).The blood UA level increased to a higher level on the 7th day of modeling,and maintained at a higher level for a long time.It decreased rapidly from the 41st day to the 48th day.The renal pathological examination showed aggravated infiltration of lymphocytes and stromal fibrous proliferation.On the 48th day of modeling,the proliferation of the fibrious tissue and the interstitial fibrosis were obvious on the bases of the aforesaid changes.The serum BUN,Cr,and blood UA obviously increased in the rats administered with 150,200,250,and 300 mg/kg when compared with the normal control group,reaching the level of chronic renal failure(P<0.05).These levels obviously decreased 17 days after restoring to normal fodder feeding,and approached the normal levels till the 35th day.ConclusionIdeal experimental animal models of gouty nephropathy complicated with chronic renal failure could be established in male Wistar rats by feeding with 10% fodder yeast and 100 mg/kg adenine by gastrogavage for 5 weeks.

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