2种建立慢性肾脏衰竭合并肾性贫血大鼠模型的方法比较

Comparision of two kinds of methods estabishing the rat model of chronic renal failure complicated with renal anemia

目的:比较5/6肾切除和腺嘌呤灌胃2种方法建立慢性肾脏衰竭(肾衰)合并肾性贫血模型对大鼠肾脏损伤的影响。方法:SD雄性大鼠20只,随机分为正常对照组和模型1、2、3组,各5只。正常对照组给予灭菌蒸馏水灌胃,每天2 mL。模型1组采用5/6肾切除法制作大鼠肾衰模型,肾切除采取Platt法。模型2、3组均采用腺嘌呤灌胃法造模,模型2组给予大鼠腺嘌呤200 mg·kg^(-1)·d^(-1)灌胃2周,第3周开始隔天灌胃,共计4周;模型3组予腺嘌呤300 mg·kg^(-1)·d^(-1)灌胃10 d,第11天起改为250 mg·kg^(-1)·d^(-1),连续灌胃11 d,共计21 d。实验第8周末,比较各组大鼠体质量、血压和血红蛋白及肾功能指标,观察大鼠肾脏病理学改变,并采用免疫组织化学法检测大鼠肾组织α-平滑肌肌动蛋白、骨桥蛋白和Ⅰ型、Ⅲ型胶原蛋白表达。结果:模型2、3组大鼠体质量均明显低于正常对照组(P<0.01);各模型组血压均有不同程度升高(P<0.05~P<0.01)。与正常对照组比较,各模型组血红蛋白均明显降低(P<0.01),血肌酐和尿素氮均升高(P<0.05~P<0.01),模型3组血尿酸水平亦升高(P<0.05)。肉眼可见各模型组大鼠肾脏形态及色泽改变。且与正常对照组大鼠比较,各模型组α-平滑肌肌动蛋白、骨桥蛋白表达均显著升高(P<0.01),Ⅰ、Ⅲ型胶原蛋白表达亦均升高(P<0.05~P<0.01)。结论:5/6肾切除法和腺嘌呤灌胃法均可制作慢性肾衰合并肾性贫血大鼠模型,可根据研究内容选择合适方法和造模药物剂量。

Objective：To compare the effects between 5 / 6 nephrectomy and adenine irrigation in establishing the rat model of chronicrenal failure complicated with renal anemia on the kidney function of rats. Methods：Twenty rats were randomly divided into the controlgroup,model 1,2 and 3 groups（5 rats each group）. The control group was irrigated with 2ml sterilized distilled water everyday,Themodel 1 was established with Platt method,the model 2 was established with 200 mg·kg- 1·d - 1adenine for 2 weeks,then one timetwo days for 2 weeks,and the model 3 were established with 300 mg·kg- 1·d - 1adenine for 10 days,then 250 mg·kg- 1·d - 1adenine for 11 days. After 8 weeks of experiment,the parameters of the body mass,blood pressure,hemoglobin and renal function,therenal pathological changes,and the expressions of smooth muscle actin,osteopontin,and type and collagen in kidney tissuedetected by immunohistochemical method between two groups were compared. Results：The body mass in model 2 and 3 groups wassignificantly lower than that in control group（P 〈 0. 01）. The blood pressure in four groups increased in varying degrees（P 〈 0. 05 to P〈 0. 01）. Compared with the control group,the levels of hemoglobin in three model groups significnatly decreased（P 〈 0. 01）,the levelof serum creatinine and urea nitrogen in model groups increased（P 〈 0. 05 to P 〈 0. 01）,and the level of of uric acid in model 3 groupincreased （P 〈 0. 05）. The renal morphology and color changes in model groups were found. Compared with control group,the levels o琢鄄smooth muscle actin,osteopontin,and type 玉 and 芋 collagen in three model groups significnatly increased（P 〈 0. 05 to P 〈 0. 01）.Conclusions：Both 5 / 6 nephrectomy and adenine can be used to establish the rat model of chronic renal failure complicated with renaanemia, and the appropriate method and drug dose should bechosen according to the purpose of the experiment.