肾性贫血动物模型的制作  

Establishmentof Animal Model of Renal Anemia

作　　者：汪杨[1,2] 李菲 尹忠[1] 魏日胞[1] WANG Yang;LI Fei;YIN Zhong(Department of Nephrology,Chinese PLA General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Disease,Beijing,100853)

机构地区：[1]解放军总医院肾脏病科,全军肾脏病研究所,肾脏疾病国家重点实验室,国家慢性肾病临床医学研究中心,肾脏疾病研究北京市重点实验室,北京100853 [2]解放军总医院第八医学中心肾脏病科,北京100091 [3]南开大学医学院,天津300071

出　　处：《中国中西医结合肾病杂志》2020年第4期289-292,I0004,I0005,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：科技部国家重点研发计划“中医药现代化研究”重点专项项目(2018YFC1704203);国家自然科学基金资助项目(No.81471027,81273968,81072914);301百项优势项目(No.YS201408)。

摘　　要：目的:应用适量马兜铃酸(aristolochic acid,AA)探索创建肾性贫血小鼠模型。方法:6周龄雄性C57BL/6小鼠分3组,正常对照组;马兜铃酸腹腔注射组:AA/2d组(马兜铃酸3 mg·kg^(-1)·2 d^(-1))和AA/3d组(3 mg·kg^(-1)·3 d^(-1)),共给药6周。造模第6、9、12周观察肾功能、贫血指标、肾脏病理评分、肾纤维化及肾组织EPO的蛋白表达情况。结果:给药6周时,血肌酐AA/2d组(29.9±1.5)μmol/L和AA/3d组(31.0±1.9)μmol/L均明显高于对照组(8.7±1.4)μmol/L,P<0.001;Hb水平AA/2d组(88.3±3.1)g/L、AA/3d组(85.7±7.4)g/L都明显低于对照组(148.7±4.9)g/L,P<0.001;HCT值AA/2d组、AA/3d组分别为0.30±0.01、0.29±0.02还是都明显低于对照组(0.51±0.02),P<0.001;肾脏病理呈现明显的肾间质纤维化,肾组织中EPO蛋白表达水平下降,提示肾性贫血模型成功。连续观察9、12周,上述变化持续存在,但AA/2d、AA/3d组间的临床病理指标无统计学意义。结论:3 mg·kg^(-1)·3 d^(-1)马兜铃酸连续给药6周可成功建立合格稳定的肾性贫血小鼠模型,该模型临床表现为不可逆的肾衰竭和贫血,肾组织中的促红素表达下降,肾脏病理表现为慢性肾间质纤维化。Objective:The application of a moderate amount of aristolochic acid to explore the establishment of a mouse model of renal anemia.Methods:6-week-old male C57BL/6 mice were divided into 3 groups:normal control group,Aristolochic acid administration group:AA/2d group:3 mg/kg aristolochic acid intraperitoneally;AA/3d group:3 mg/kg aristolochic acid intraperitoneally,once every 3 days.The administration time for mice is 6 weeks.Changes in renal function,blood routine,renal pathological scores,renal fibrosis,and EPO protein expression in renal tissues were recorded.Results:At the 6th week of administration,the serum creatinine in the AA/2d group(29.9±1.5)μmol/L and the AA/3d group(31.0±1.9)μmol/L were significantly higher than this in the control group(8.7±1.4)μmol/L,P<0.001.The Hb levels in the AA/2d group(88.3±3.1)g/L and AA/3d group(85.7±7.4)g/L were significantly lower than those in the control group(148.7±4.9)g/L,P<0.001;HCT of AA/2d group and AA/3d group were 0.30±0.01 and 0.29±0.02 respectively,which were also significantly lower than those of control group(0.51±0.02),P<0.001.Renal pathology showed obvious renal interstitial fibers.The level of EPO protein in kidney tissue was decreased.These changes were observed continuously for 12 weeks.However,the clinical and pathological indicators between AA/2d and AA/3d group had no statistical significance.Conclusion:These results suggested that the intraperitoneal injection of AA at a dosage of 3 mg/kg every 3 days for 6 weeks can successfully induce renal anemia in mice.The model shows renal interstitial fibrosis and anemia,and the expression of erythropoietin in tissues decreases.

关 键 词：肾性贫血 马兜铃酸 肾间质纤维化 促红细胞生成素 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]