中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (8): 1207-1211.doi: 10.3969/j.issn.2095-4344.3048

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

高脂高糖饮食结合链脲佐菌素建立2型糖尿病性骨质疏松症大鼠模型

唐  辉1，姚志浩1，罗道文1，彭双麟2，杨双林2，王  浪2，肖金刚1，2，3   

  1. 1西南医科大学口腔医学院，四川省泸州市   646000；2西南医科大学口颌面修复重建和再生实验室，四川省泸州市   646000；3西南医科大学附属医院口腔颌面外科，四川省泸州市   646000
  • 收稿日期:2020-06-03 修回日期:2020-06-05 接受日期:2020-07-09 出版日期:2021-03-18 发布日期:2020-12-11
  • 通讯作者: 肖金刚，博士，教授，西南医科大学口腔医学院，四川省泸州市 646000；西南医科大学口颌面修复重建和再生实验室，四川省泸州市 646000；西南医科大学附属医院口腔颌面外科，四川省泸州市 646000
  • 作者简介:唐辉，男，1992年生，重庆市人，西南医科大学在读硕士，主要从事口腔颌面外科临床与基础研究。
  • 基金资助:
    国家自然科学基金项目(81870746，81371125)

High fat and high sugar diet combined with streptozotocin to establish a rat model of type 2 diabetic osteoporosis

Tang Hui1, Yao Zhihao1, Luo Daowen1, Peng Shuanglin2, Yang Shuanglin2, Wang Lang2, Xiao Jingang1, 2, 3   

  1. 1School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Oral and Maxillofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 3Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Received:2020-06-03 Revised:2020-06-05 Accepted:2020-07-09 Online:2021-03-18 Published:2020-12-11
  • Contact: Xiao Jingang, MD, Professor, School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Oral and Maxillofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • About author:Tang Hui, Master candidate, School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81870746 and 81371125

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摘要：

文题释义：
糖尿病性骨质疏松症(diabetic osteoporosis，DOP)：是一种退行性、全身性、代谢性疾病，为糖尿病在骨骼系统的常见慢性并发症之一，因胰岛素缺乏或胰岛素抵抗引起骨代谢及钙磷代谢紊乱，导致单位体积内骨量减少、骨组织微结构改变、骨强度减低、脆性增加，易发生骨折。
链脲佐菌素(Streptozotocin，STZ)：是从无色链霉菌中提取的一种广谱抗生素，具有抗菌、抗肿瘤的作用，本质是一种氨基葡萄糖-亚硝基脲。由于其对动物胰岛β细胞具有特异性的毒性作用，被广泛用于1型和2型糖尿病动物模型制备。

背景：单纯给予高脂高糖饮食诱导建立糖尿病骨质疏松症模型时间较长，费用高，成模稳定性较差。化学药物链脲佐菌素诱导法就被作为研究绝经后骨质疏松的动物模型建立的最常用方法之一，目前对于该疾病模型的鉴定报道较少。
目的：建立大鼠2型糖尿病性骨质疏松模型，并对建立的2型糖尿病大鼠骨质疏松动物模型进行鉴定。
方法：选择7周龄雄性 SD 大鼠32只，根据体质量采用随机数字表法将其随机分为对照组(16只)和模型组(16只)，模型组采用高脂高糖饲料喂养4周，并且按35 mg/kg一次性腹腔注射链脲佐菌素诱导成为2 型糖尿病性骨质疏松症模型；对照组采用普通饲料喂养4周，并且按10 mL/kg腹腔注射等剂量柠檬酸-柠檬酸钠缓冲液。从形态学、组织学、影像学等几方面对两组大鼠进行研究。实验方案经西南医科大学动物实验伦理委员会批准。
结果与结论：①模型组16只大鼠成模12只，成模率75%；②与对照组大鼠比较，模型组大鼠在注射链脲佐菌素后，体质量呈现出先下降、后稍回升的趋势；大鼠表现出多饮、多尿、多食等糖尿病症状；空腹血糖明显升高(P < 0.05)，并呈持续状态；股骨组织学切片可见骨小梁稀疏；胫骨Micro-CT扫描及三维重建显示大鼠骨体积分数及骨小梁数量显著降低，骨小梁分离度显著升高，出现明显骨质疏松影像；③结果可说明，选取的7周龄SD大鼠在高糖高脂饲料喂养 4 周基础上，联合采用小剂量链脲佐菌素(35 mg/kg)，可以成功建立2 型糖尿病性骨质疏松症大鼠模型。从形态学、组织学、影像学等几方面可以确定糖尿病性骨质疏松症模型的建立。

https://orcid.org/0000-0003-1657-8571(唐辉) 
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 骨, 骨质疏松, 糖尿病, 链脲佐菌素, Micro-CT, 模型, 大鼠

Abstract: BACKGROUND: A high-fat and high-sugar diet to induce a diabetic osteoporosis model is time-consuming, with high cost and poor model stability. Induction by streptozotocin is one of the most common methods to establish an animal model of postmenopausal osteoporosis. At present, there are few reports on the identification of this disease model.
OBJECTIVE: To establish a rat model of type 2 diabetic osteoporosis rat models, and to identify the animal model established.
METHODS: Thirty-two male 7-week-old Sprague-Dawley rats were selected and randomly divided into a normal control group (n=16) and a model group (n=16) according to their body mass using a random number table method. The model group was fed with high-fat and high-sugar diet for 4 weeks, and a small dose of streptozotocin was intraperitoneally injected at 35 mg/kg to induce a type 2 diabetic osteoporosis model; the normal control group was fed with normal maintenance feed for 4 weeks, and an equal dose of 10 mL/kg citric acid-sodium citrate buffer was intraperitoneally injected. Two groups of rats were studied from the aspects of morphology, histology and imaging. An approval was obtained from the Animal Experimental Ethics Committee of Southwest Medical University. 
RESULTS AND CONCLUSION: There were 16 rats in the model group, 12 rats were modeled, and the modeling rate was 75%. Compared with the normal control group, in the model group, the body mass of rats showed a gradual downward trend and a slightly upward trend after the injection of streptozotocin. These rats presented symptoms of diabetes, such as polydipsia, polyuria and polyphagia. Fasting blood glucose level increased significantly (P < 0.05), and showed a continuous state. The histological section showed that the trabecular bone was sparsely distributed. Imaging results showed that the bone volume fraction and the number of trabeculae in rats were significantly reduced, and the separation of trabecular bone was significantly increased, indicating a significant osteoporosis. To conclude, the 7-week-old Sprague-Dawley rats which are fed with high-sugar and high-fat diet for 4 weeks can be given low-dose streptozotocin (35 mg/kg) to successfully establish the animal model of type 2 diabetic osteoporosis. From the aspects of morphology, histology, imaging, the successful establishment of diabetic osteoporosis model can be determined.

Key words: bone, osteoporosis, diabetes, streptozotocin, Micro-CT, model, rat

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