慢性肾功能不全小鼠动物模型的建立

Establishment of an Animal Model for Chronic Renal Insufficiency

目的 建立一种小鼠肾功能不全动物模型。方法 选取雄性小鼠随机分为正常对照组、模型小剂量组 (腺嘌呤 30 0mg kg)和模型大剂量组 (腺嘌呤 6 0 0mg kg)。每组 6 0只动物 ,按 0 .1ml 10g体重分别灌胃给药 3d ,每天 1次 ,正常对照组给予蒸馏水 ,模型组按上述药量给予腺嘌呤。分别在给药第 7,2 1及 35天各组随机取材 ,眼眶取血 ,分离血清进行BUN及肌酐含量测定。取肾脏常规石蜡包埋 ,HE染色 ,观察病理改变。结果 血清BUN造模后 35d各模型组仍显著高于对照组 2倍以上。肌酐在 7d及 2 1d时均显著高于对照组 ,但 35d时与对照组差异已无显著性。造模后 2 1及 35d取材组织改变基本相同 ,可见肾脏肥大苍白 ,表面凹凸不平显著 ,重量增加。镜下可见 :间质有炎细胞侵润 ,出现泡沫细胞 ,肾小球萎缩 ,分界不清 ,肾小管有蛋白管型 ,钙盐沉积 ,小剂量相对轻微。结论 腺嘌呤 30 0及 6 0 0mg kg灌胃给药 3d ,小鼠肾脏组织可出现明显的肾小球及肾小管损害 ,同时有氮质血症 ,营养不良 ,与人类慢性肾功能不全患者的表现非常相似。

Objective To make mice as a model of chronic renal insufficiency. Methods Male mice were randomly divided into three groups,that is, normal control group , low dose model group （adenine,300 mg/kg)and high dose model group（adenine,600 mg/kg).There were 60 mice in each group.The control was treated orally with distilled w ater (0.1ml/10g)，once a day for 3 days.The model was given adenine at a dose me ntioned above.Samples were randomly obtained from each group on the 7th,21th and 35th day after dosing.Blood was taken from eye socket and serum was separated f or measuring the content of blood urea nitrogen(BUN) and creatine(Cr).The paraff in embedded kidney tissues were stained with haemafin and eosine(HE) for observa tion of morphological changes. Results BUN of each model group was two times higher than that of the control on the 35th day after modelling.Cr was significantly higher than the control on the 7th and 21th day,however,no significant diffenence was observed on the 35th day.There were almost the same pathological changes between the 21th day and 35th day after modelling. The kidney with a gai n in weight was hypertrophic,pallid and rough.Observation under li ght microscope showed:inflammatory cells infiltration in peritubular， emersion of foam cells,atrophy of glomerulus,vagueness of boundary,tubular protein in ren al tubules,calcareous deposit. However, the morphological changes were much slig hter in low-dose model group. Conclusions There were significant lesions of glomerulus and tubules in mice with nitremia and dystrop hy after orally dosing for 3 days.It was exactly the same as those patients with chronic renal insufficiency.It showed that the mice treated with adenine could be made as a model of renal dysfunction.