糖脂代谢病大鼠模型的构建及评价
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首都医科大学附属北京中医医院

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基于异病同治理论从菌群代谢产物TMAO介导的PERK/FoxO1和PI3K/Akt信 号通路探讨清血消脂方改善糖脂代谢病的作用机制


Construction and Evaluation of a Rat Model for Glycolipid Metabolic Disorder
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Beijing Hospital of Traditional Chinese Medicine,Capital Medical University

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Based on the theory of treating different diseases with the same treatment, the mechanism of Qingxue Xiaozhi on glucolipid metabolism diseases was explored from the PERK/FoxO1 and PI3K/Akt signaling pathway mediated by the flora metabolite TMAO

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    摘要:

    目的 本研究旨在通过饲喂Purina 5008饲料诱导Zucker糖尿病肥胖(Zucker Diabetic Fatty,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大鼠为模型组(n=9),Zucker瘦型(Zucker Lean,ZL)大鼠为正常对照组(n=9)。模型组喂饲Purina 5008饲料,对照组喂饲普通饲料,持续7周。观察大鼠体征评分、体重、Lee's指数、进食量及饮水量变化;测定空腹血糖、口服葡萄糖耐量、血清总胆固醇(Total cholesterol,TC)、甘油三酯(Triglycerides,TG)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(High-density lipoprotein cholesterol,HDL-C)、丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、胰岛素水平及胰岛素抵抗指数(Homeostasis model assessment of insulin resistance,HOMA-IR);通过苏木精 伊红(Hematoxylin eosin,H E)染色和油红O(Oil Red O,油红O)染色分析肝脏、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、粪质变软等体征,且体征评分显著升高(P<0.01)。模型组体重、Lee"s指数、进食量和饮水量均显著增加(P<0.01),空腹血糖、血清TC、TG、LDL-C、ALT、AST及HOMA-IR水平显著升高(P<0.01)。病理学检测显示,模型组肝脏脂肪变性严重,胰腺胰岛细胞空泡样变,主动脉壁结构紊乱呈不均匀增厚。结论 通过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病理特征,包括糖脂代谢紊乱、胰岛素抵抗及多器官损伤,为糖脂代谢病的机制研究与药物评价提供了可靠的实验平台。

    Abstract:

    Objective This study aimed to establish a glycolipid metabolic disorder model in Zucker Diabetic Fatty (ZDF) rats induced by Purina 5008 feed and systematically 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 (n=9), and Zucker Lean (ZL) rats served as the normal control group (n=9). The model group was fed Purina 5008 feed, while the control group received standard feed for 7 weeks. Observations included physical sign scores, body weight, 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 via hematoxylin eosin (H E) and Oil Red O staining. Results Compared to the control group, the model group exhibited significant increases in physical sign scores (P<0.01), including polydipsia, polyphagia, dull fur, and soft feces. Body weight, Lee’s index, food/water intake, fasting blood glucose, serum TC, TG, LDL-C, ALT, AST, and HOMA-IR were markedly elevated (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. Conclusion The ZDF rat model induced by Purina 5008 feed stably simulates core pathological features of glycolipid metabolic disorders, including metabolic dysregulation, insulin resistance, and multi-organ damage, offering a reliable platform for mechanistic studies and therapeutic evaluation.

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  • 收稿日期:2025-04-21
  • 最后修改日期:2025-07-11
  • 录用日期:2025-12-29
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