改良的肥胖大鼠模型的建立及其肾脏病理特点

目的高脂饲料喂养诱导肥胖大鼠模型的建立,观察其肾脏病变特点。方法 60只雄性Wistar大鼠高脂饲料喂养2周后,根据体重增长排序,剔除位于下1/3大鼠,留取上2/3大鼠,随机分为两组：对照组（NC组,n=20）给予普通饲料;模型组（ORG组,n=20）给予高脂饲料。喂养12周,观察大鼠体重、体长、Lee＇s指数、尾动脉血压、空腹血糖（fasting blood-glucose,FBG）、血脂、空腹胰岛素（fasting insulin,FINS）、胰岛素抵抗指数（homeostasis model assessment of insulin resistance,HOMA-IR）、瘦素（leptin,LEP）及24 h尿白蛋白变化;测定大鼠附睾脂肪质量,计算脂体比;计算大鼠附睾脂肪细胞数目并测量直径大小;观察大鼠肾脏病理变化。结果 12周末,与NC组比较,ORG组大鼠体重、体长、Lee＇s指数增加显著（P〈0.01）;尾动脉血压、FBG、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）升高（P〈0.01）;高密度脂蛋白胆固醇（HDL-C）两组间的差异无统计学意义（P〉0.05）。FINS、HOMA-IR及LEP均显著升高（P〈0.01）;24 h尿白蛋白增加（P〈0.01）;附睾脂肪质量增加,脂体比值增大,脂肪细胞数目增多,体积增大（P〈0.05）;肾小球增大（P〈0.01）,肾小球囊腔变窄（P〈0.01）。结论高饲料结合改良的饲养方法可高效制备出肥胖大鼠模型,其肾脏病理符合肥胖相关性肾病早期病变的特点。

Obese rat modeling and its features of renal pathology

Objective To establish an obese rat model induced by high-fat diet and observe its features of renal involvement. Methods Firstly, in order to exclude obesity-resistant rats, 60 male Wistar rats were fed with high-fat diet for 2 weeks, then sorted according to their weight growth, the upper 2/3 rats were randomized to two groups, normal control group （NC group, 20 rats） fed with ordinary diet, model group （ORG group, 20 rats） fed with high-fat diet, both for 12 weeks. The following indicators were measured： body weight, body length, Lee＇s index, tail artery blood pressure, fasting blood-glucose （FBG）, serum lipid, fasting insulin （FINS）, homeostasis model assessment of insulin resistance （HOMA-IR）, leptin （LEP）, 24 hours urine albumin, epididymis fat mass, fat-body mass ratio, adipocyte number and adipocyte size. Renal histopathologic changes were observed as renal lesion indicators. Results After 12 weeks, compared with NC group, the body weight, body length and Lee＇s index of ORG group were significantly higher （P〈0.01）, the rat tail artery blood pressure, FBG, triglycerides, total cholesterol, low-density lipoprotein of ORG group were significantly higher （P〈0.01）, the difference of high-density lipoprotein between the two groups had no statistical significance （P〉0.05）, FINS, HOMA-IR and LEP were higher （P〈0.01）, epididymis fat mass, fat-body mass ratio, adipocyte number and adipocyte size of ORG group were higher than NC group, and the differences were statistically significant （P〈0.05）. Compared with NC group, ORG group＇s 24 hours urine albumin was higher （P〈0.01）, Bowman＇s capsule cavity was larger （P〈 0.01）, basement membrane was thicker （P〈 0.01）. Conclusion High-fat diet with improvement of breeding method was proved to be an effective way to make obese rat model, which may provide an early-stage obesity-related nephropathy features.