糖脂代谢病大鼠模型的构建及评价
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1. 首都医科大学附属北京中医医院,北京 100010;2. 北京市中医药研究所,北京 100010

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Construction and evaluation of a rat model for glycolipid metabolic disorder
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1. Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, China;2. Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China

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    目的 本研究旨在通过 Purina 5008 饲料诱导 ZDF 大鼠构建糖脂代谢病模型,并系统评估其病理特征,为糖脂代谢病机制研究及药物开发提供临床前模型工具。 方法 选取 12 周龄雄性 ZDF 大鼠(模型组,n= 9)和 ZL 大鼠(正常对照组,n=9)。 模型组喂饲 Purina 5008 饲料,正常对照组喂饲维持饲料,持续 7周。 观察大鼠体征、体质量、Lee’s 指数、进食/ 饮水量;测定空腹血糖、口服葡萄糖耐量、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、胰岛素水平及 HOMA-IR;通过苏木素-伊红(HE)和油红 O 染色分析肝、胰腺及主动脉的病理改变。 结果 与正常对照组相比,模型组大鼠出现多饮多食、被毛暗淡等典型体征(P<0. 01),体质量、Lee’s 指数、进食/ 饮水量显著增加( P<0. 01),空腹血糖、血脂及 HOMA-IR 水平均显著升高( P<0. 01)。 病理显示,肝脂肪变性严重,胰腺胰岛细胞空泡样变,主动脉壁结构紊乱增厚。 结论 Purina 5008 饲料诱导的 ZDF 大鼠模型可稳定模拟糖脂代谢病的核心特征,包括糖脂代谢紊乱、胰岛素抵抗及多器官损伤,为机制研究与药物评价提供了可靠的实验平台。

    Abstract:

    Objective To establish a model of glycolipid metabolic disorder model in Zucker diabetic fatty (ZDF) rats induced by Purina 5008 feed, and to evaluate its pathological characteristics to provide a preclinical model tool for mechanistic research and drug development. Methods Twelve-week-old male ZDF rats were selected as the model group and Zucker lean(ZL) rats served as the normal control group (n= 9 rats per group). Rats in the model group were fed Purina 5008 feed, while normal control rats received standard feed for 7 weeks. Observations included physical sign scores, body mass, Lee’ s index, food and water intake, fasting blood glucose, oral glucose tolerance, serum total cholesterol ( TC), triglycerides ( TG), low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C), alanine aminotransferase ( ALT), aspartate aminotransferase ( AST),insulin levels, and homeostasis model assessment of insulin resistance ( HOMA-IR). Pathological changes in the liver, pancreas, and aorta were analyzed by hematoxylin-eosin(HE) and oil red O staining. Results Compared with the normal control group, model rats showed typical signs such as excessive drinking and eating, dull hair ( P<0. 01), and their body mass, Lee’s index, food / water intake increased significantly (P<0. 01), and fasting blood glucose, blood lipid and HOMA-IR all increased significantly (P<0. 01). Pathological examination revealed severe hepatic steatosis, vacuolar degeneration of pancreatic islet cells, and disorganized aortic wall structure with uneven thickening in the model group. Conclusions A ZDF rat model induced by Purina 5008 feed can stably simulate the core pathological features of glycolipid metabolic disorders, including metabolic dysregulation, insulin resistance, and multi-organ damage, offering a reliable platform for future mechanistic studies and therapeutic evaluation.

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张萌,郭子轩,张蕾,周明学,李思耐,刘卫红.糖脂代谢病大鼠模型的构建及评价[J].中国实验动物学报,2026,34(1):1~9.

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  • 收稿日期:2025-04-21
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  • 在线发布日期: 2026-03-05
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