实验动物与比较医学 ›› 2011, Vol. 31 ›› Issue (3): 160-165.DOI: 10.3969/j.issn.1674-5817.2011.03.002

• 论著 • 上一篇    下一篇

实验性Ⅱ型糖尿病大鼠模型复制方法的改进及其评价

汪凌云1, 汪萍2, 孙玉秀1, 李丹丹1, 刘嵩1, 章秋2, 鲁云霞1   

  1. 1.安徽医科大学生物化学教研室, 合肥 230032;
    2.安徽医科大学第一附属医院内分泌科, 合肥 230022
  • 收稿日期:2010-11-17 出版日期:2011-06-25 发布日期:2011-06-25
  • 作者简介:汪凌云(1987-), 女, 在读硕士研究生。目前从事专业: 糖尿病的分子生物学。E-mail: jingdewly@yahoo.com.cn
  • 基金资助:
    安徽省教育厅自然科学基金(2006KJ371B)

Development and Evaluation of a Modeling Method For Experimental Rat with Type 2 Diabetes Mellitus

WANG Ling-yun1, WANG Ping2, SUN Yu-xiu1, LI Dan-dan1, LIU Song1, ZHANG Qiu2, LU Yun-xia1   

  1. 1. Dept of Biochemistry, Anhui Medical University, Hefei 230032,China;
    2. Dept of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022,China
  • Received:2010-11-17 Online:2011-06-25 Published:2011-06-25

摘要: 目的 建立一种快速简便的Ⅱ型糖尿病(T2DM)大鼠模型并观察其胰岛及肾脏的病理学变化。方法 雄性SD大鼠随机分为3组: (1)对照组,尾静脉注射0.1 mol/L柠檬酸缓冲液,普通饲料喂养; (2)鸡蛋饲料组,尾静脉注射0.1 mmol/L柠檬酸缓冲液,50%鸡蛋饲料喂养; (3)模型组,尾静脉一次性注射30 mg/kg 链脲佐菌素(STZ),50%鸡蛋饲料喂养。4周后所有大鼠进行口服糖耐量实验(OGTT)。测定24 h尿微量白蛋白(U-ALB)和尿肌酐(U-CREA)水平。采血测定空腹血糖(FBG)、胰岛素(Fins)、血脂(TG和TC、FFA)、SOD、MDA水平。免疫组化染色观察胰岛β细胞的形态学改变。左肾称重并计算肾脏指数(KI),右肾进行病理学观察。结果 与对照组比较,模型组大鼠的体重增加(P<0.05),FBG、Fins、TG、TC、FFA、MDA水平升高(P<0.05),SOD水平、ISI显著降低(P<0.05)。胰岛体积明显变小,散在分布。24 h尿液、U-ALB、U-CREA和KI均增加(P<0.05),光镜和电镜结果表明肾小球毛细血管基底膜不均匀增厚,足突大部分增宽融合,说明该模型还伴有早期的肾脏损害。结论 该方法成功地制备了T2DM大鼠模型,STZ用量少,饲料配制方便,时间短,成模率高,死亡率低,可用于T2DM及其慢性并发症糖尿病肾病(DN)的发病机制及治疗的研究。

关键词: Ⅱ型糖尿病, SD大鼠, 链脲佐菌素, 50%鸡蛋饲料, 胰岛素抵抗

Abstract: Objective To establish a fast and convinient type 2 diabetes mellitus (T2DM) rat model. Methods Six-week-old male SD rats were randomly allocated into three groups: normal control group, egg-diet group and model group. The model rats were injected intraperitoneally with 30 mg/kg streptozotocin (STZ), then fed egg-diet for 4 weeks to induce diabetes. NC group rats were fed normal chow diet for 4 weeks. Egg-diet group rats were fed egg-diet for 4 weeks. Islet function in each group was evaluated by oral glucose tolerance test (OGTT). 24hr urine specimen was collected and used to analyze urinary albumin and creatinine content. The serum biochemical indices such as FBG, FIns, TG, TC, FFA, SOD, MDA levels were measured. Islets were examined with immunohistochemical analysis of insulin. Kidneys were evalutated with HE staining and transmission electron microscopy respectively. Results Compared with NC rats, the body weight in model group and egg-diet group was increased markedly. Levels of FBG, FIns, TG, TC, MDA in model groups were increased significantly, while SOD levels and ISI values were decreased significantly. 24hr urine excretion, urine albumin and creatinine level in model group were all increased markedly. The pancreatic islets appeared smaller significantly in model group than in NC group. The kidneys in model rats became hypertrophic and kidney indices were increased significantly than in NC rats. Pathological examination showed that basilar membrane in model rats became asymmetrical thicken, foot protrusions became widen and fused mutually. Conclusions This method for improving T2DM rat model was high-efficient, stable and had low death rate, suitable for studying the mechanism and therapy of type 2 diabete mellitus and its chronic complications especially diabetic nephropathy.

Key words: Type 2 diabetes mellitus, SD rats, Streptozotocin, Egg diet, Insulin resistance

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