高脂喂养加单侧肾切除制作小鼠糖尿病肾病模型研究

目的 探讨高脂喂养加单侧肾切除制作糖尿病肾病（DN）模型的可行性.方法 8 周龄的MKR 小鼠（骨骼肌特异性Insulin/IGF-1 双受体缺失的转基因小鼠）60 只,雌雄各半,随机分为3 组,每组20 只.空白组（基础饲料喂养）,高脂组（高脂饲料喂养）,模型组（高脂饲料喂养＋单侧肾切除组）.造模后第1、2、4、6、8 周测体质量、空腹血糖、尿微量白蛋白（UmAlb）.8 周后心脏采血处死各组小鼠留取血标本及肾组织分别进行血肌酐（Cr）、血尿素氮（BUN）的检测及光镜和电镜下观察肾脏病理学改变.结果 与空白组比,8 周时,高脂组、模型组两组血糖明显升高（P〈0.01）,而两组之间比较,血糖无明显变化（P〉0.05）.模型组UmAlb、Cr、BUN 较空白组、高脂组明显升高,差异有显著统计学意义（P〈0.01）,且肾质量（KW）,肾/体质量（KW/BW）较空白组显著增大,病理变化明显.结论 高脂饲料喂养加单侧肾切除的MKR 小鼠是一个良好的糖尿病肾病模型.

Establishment of diabetic nephropathy mouse model by high fat diet feeding combined with unilateral nephrectomy

Objective To explore the possibility of progressive diabetic nephropathy mouse model by high fat diet feeding combined with unilateral nephrectomy. Methods Sixty 8-week-old transgenic MKR mice who were deficient in IGF-1 receptor and insulin receptor in skeletal muscle were randomly divided into three groups including ordinary feed group, high fat feed group, high-fat diet feed combined with unilateral nephrectomy model group. The body weight, fasting blood glucose （FBG）, micro albumin of urine（UmAlb） were detected at 1st, 2nd, 4th, 6th, 8th week after modeled. Eight weeks later, all mice were put to death, and blood and kidney were prepared, then the serum BUN and Cr were detected and the pathologic changes were observed under the light and electron microscope. Results Compared with ordinary feeding group, FBG in high fat feed group and model group was increased significantly at 8th week （P 〈0.01）. However, there were no differences between high fat feeding group and model group in terms of FBG （P〉0.05）. BUN, Cr and urine UmAlb in model group were increased significantly compared with those of ordinary feeding group and high fat feeding group. Compared with ordinary feed group, the kidney weight（KW） and the kidney/body weight（KW/BW） of model group were increased（P〈0.01）, and the renal pathological lesions of mice in model group were obvious. Conclusion The diabetic nephropathy mouse model can be established by treated MKR with high-fat diet feeding combined with unilateral nephrectomy.