尿毒症加速性动脉粥样硬化模型的建立和评价  

Establishment and evaluation of uremic atherosclerosis models in ApoE^(-/-) mice

作　　者：余洁[1] 赵景宏[2] 邓梦扬[1] 黄岚[1] 

机构地区：[1]第三军医大学新桥医院全军心血管病研究所,重庆400037 [2]第三军医大学新桥医院全军肾脏病中心,重庆市肾病研究所,重庆400037

出　　处：《第三军医大学学报》2009年第19期1862-1865,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30700316);重庆市自然科学基金(2007BB5024)~~

摘　　要：目的探索短时间内建立尿毒症加速性动脉粥样硬化动物模型的方法,并评价其相关指标。方法6周龄雄性apoE-/-小鼠70只,分为模型组和假手术组,每组35只;另35只6周龄雄性C57小鼠作为对照组,均饲以高脂饲料。模型组、C57组小鼠行肾大部损毁术,建立尿毒症加速性动脉粥样硬化动物模型,假手术组施行假手术。分别于右肾皮质电烙术后0、2、4、6周和8周末,检测血尿素(Urea)、总胆固醇(TC)和甘油三酯(TG)水平。同时取小鼠主动脉弓部进行病理检测;测定粥样硬化斑块面积及斑块面积分数。结果肾大部损毁术后6周,模型组尿素、TC、TG水平较假手术组分别增高188.3%、40.8%、29.8%(P<0.01),且主动脉粥样斑块面积较对照组增大了1.3倍(P<0.05),斑块面积分数显著增高(P<0.01)。结论尿毒症可显著加速动脉粥样硬化进程,利用apoE-/-小鼠行肾脏大部损毁术可以建立尿毒症加速性动脉粥样硬化动物模型。Objective To establish uremic atherosclerosis models in apoE ^-/- mice and evaluate its feasibility. Methods Totally 70 6-week-old male apoE^-/- mice were randomized into 2 groups, uremic group （n = 35 ） and nonuremic control group （n = 35 ）. All mice were fed with a Western diet. Uremic group mice underwent partial kidney ablation with electrocoagulation of right renal cortex followed by left total nephrectomy in 2 weeks later and control animals underwent sham operation. Serum levels of urea, total cholesterol and triglycerides were assessed at 0, 2, 4, 6 and 8 weeks after the first surgery. The cross-section surface area of the lesion and the lesion area fraction were assessed. Results At 6 weeks after nephrectomy, the level of serum urea in chronic renal failure （CRF） mice was 188.3% higher than that of control mice, and total cholesterol and triglyceride concentrations were increased by 40.8% and 29.8% than those of nonuremic controls, respectively （P 〈0.01 ）. Aortic plaque area of CRF groups was increased 1.3-fold compared with nonuremic controls （P 〈0.05）. Moreover, the lesion area fraction of uremic apoE^-/- mice was markedly increased when compared with controls （P 〈0.0l）. Conclusion These findings demonstrate that CRF aggravates atheroselerosis and the uremic atheroselerosis models can be established with partial kidney ablation on apoE^-/- mice. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the disease.

关 键 词：尿毒症加速性动脉粥样硬化 APOE^-/-小鼠 肾大部损毁术 

分 类 号：R-332[医药卫生] R543.506