2型糖尿病大鼠骨质疏松模型的建立  

Establishing a rat model of type 2 diabetes: its bone metabolism level

作　　者：张燕[1] 杨秋萍[2] 赵燕[1] 赵豫梅[1] 谭洪[1] 杜思成[1] 

机构地区：[1]昆明医科大学第一附属医院糖尿病科,云南省昆明市650032 [2]昆明医科大学第一附属医院干部病房科,云南省昆明市650032

出　　处：《中国组织工程研究》2016年第40期6041-6047,共7页Chinese Journal of Tissue Engineering Research

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项(2013FZ270);昆明医科大学研究生创新基金(2014N04)~~

摘　　要：背景:目前认为长期高血糖、降糖药物的使用、饮食控制、雌激素、胰岛素样生长因子、瘦素、体质量、性别、年龄等因素可能在糖尿病发生骨质疏松的病理生理过程中起着重要作用。目的:建立2型糖尿病骨质疏松模型,探讨2型糖尿病对骨代谢的影响。方法:雄性SD大鼠采用高脂高糖饮食联合小剂量链脲佐菌素(35 mg/kg)诱导2型糖尿病大鼠模型为糖尿病组;对照组予相同剂量的柠檬酸-柠檬酸钠缓冲液一次性左下腹腔注射作为正常对照组。成模4周后,糖尿病组7只,正常对照组13只进入结果分析。采用双能X射线检测大鼠骨密度,检测血清空腹血糖、胆固醇、三酰甘油、血钙、血磷、碱性磷酸酶、空腹胰岛素、骨钙素、Ⅰ型胶原交联C末端肽,观察骨形态学变化。结果与结论:与正常对照组比较,(1)糖尿病组大鼠体质量下降、空腹血糖明显升高(P<0.05),并呈持续状态;(2)糖尿病组大鼠血胆固醇、三酰甘油、空腹胰岛素、碱性磷酸酶、胰岛素抵抗指数明显升高,而胰岛素敏感指数下降(P<0.05);(3)糖尿病组血清磷、血钙、骨钙素、Ⅰ型胶原交联C末端肽,差异无显著性意义(P>0.05);(4)苏木精-伊红染色显示糖尿病组大鼠骨小梁稀疏,数量减少,间隙增大,小梁变细,连续性破坏,常见游离断增多;(5)糖尿病组全身骨密度、腰椎+双股骨+盆骨骨密度,胸腰椎骨密度均明显下降(P<0.05)。(6)结果说明,高糖高脂喂养5周基础上联合小剂量链脲佐菌素(35 mg/kg)可以诱导2型糖尿病大鼠模型。该模型具有高糖、高脂、胰岛素抵抗及骨密度下降,骨形态学检查呈骨吸收增加改变的特点。BACKGROUND： Diabetes mellitus can give rise to bone metabolic disorders that may involve long-term hyperglycemia, hypoglycemic agents, diet control, estrogen, insulin-like growth factor, leptin, body mass, sex and age. OBJECTIVE： To establish type 2 diabetic rat models, and to explore the influence of type 2 diabetes on bone metabolism. METHODS： High-fat and high-glucose diets combining with 35 mg/kg streptozotocin were used to induce type 2 diabetic model in seven male Sprague-Dawley rats （diabetic group）. Thirteen rats in control group were given intraperitoneal injection of the same amount of citric acid and sodium citrate buffer. At 4 weeks after modeling, the bone density of rats was serum detected by dual-energy X-ray, levels of fasting blood-glucose, cholesterol, triacylglycerot, serum calcium, phosphate, alkaline phosphatase, fasting insulin osteocalcin and C-terminal telopeptide-I were measured, and morphology of bone was observed. RESULTS AND CONCLUSION： Compared with control group, （1） the rat body mass and fasting blood-glucose kept on an overt rise in the diabetic group （P 〈 0.05）; （2） levels of cholesterol, triacylglycerol fasting insulin and alkaline phosphatase, as well as insulin resistance index were significantly increased, but insulin sensitivity index was significantly decreased in the diabetic group （P 〈 0.05）. （3） There were no significant differences in the levels of serum calcium, phosphate, alkaline phosphatase, osteocalcin and C-terminal telopeptide-I between two groups （P 〉 0.05）. （4） In the diabetic group, thinner and sparse bone trabeculae were split presenting more free broken ends; （5） the bone density in lumbar spine, double femoral, pelvic and thoracotumbar spine were all significantly decreased （P 〈 0.05）. （6） In conclusion, the type 2 diabetic rat model can be successfully induced by 5-week feeding high-fat and high-glucose diets combining with intraperitoneal injection of 35 mg/kg streptozotocin; these mode rats hold

关 键 词：实验动物 内分泌系统损伤与修复动物模型 骨形态 

分 类 号：R318[医药卫生—生物医学工程]