两种Ⅱ型糖尿病降糖药物效果的对比

发布时间：2018-03-18 16:01

本文选题：Ⅱ型糖尿病　切入点：ZDF大鼠　出处：《上海交通大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的本试验的目的是利用二肽激肽酶抑制剂:西他列汀,ZDF大鼠及正常SD大鼠动物模型,测试西他列汀的降血糖作用及效果,对比匹格列酮对于ZDF大鼠降血糖作用的效果,以及通过口服葡萄糖耐受实验(OGTT)测试西他列汀对于动物糖耐量的改善作用。方法4-6周龄的雄性ZDF大鼠随机分成3组(n=6),分别为溶媒组,匹格列酮组,西他列汀组。连续口服给药2周,并在第15天,第25天进行OGTT测试,检测0,30,60和120分钟血糖。第25天OGTT结束后,动物被安乐死,取肝脏,肾脏,附睾脂肪,棕色脂肪,比目鱼肌,腓肠肌,称重并计算脏器系数。采取血样,测定动物总胆固醇,甘油三酯,自由脂肪酸和高密度脂蛋白C。每周测定一次空腹6小时血糖,每天测定耗食量及动物体重。40只6-8周龄雄性Sprague Dawley大鼠,适应环境至少5天,在实验开始前一天测定餐后血糖水平,并称体重,根据血糖和体重结果,随机将动物分成4组(溶媒组、西他列汀10、60、100mg/kg组)。随后动物过夜禁食,测空腹血糖,体重并计算给药、给糖体积。-30分钟测血糖并给药,给药后30分钟给糖并测血糖,随后检测15,30,60,120分钟血糖。结果经过匹格列酮和西他列汀治疗的ZDF大鼠,空腹6小时血糖有显著的下降。治疗组体重均有不同程度增长,但进食量相似无显著性差异。治疗组动物的胆固醇,甘油三酯和高密度脂蛋白有不同程度下降。口服葡萄糖耐受实验显示,西他列汀和匹格列酮都具有改善ZDF大鼠糖耐量的作用。匹格列酮治疗的ZDF大鼠的肝脏及肾脏的脏器系数低于其他组,差异显著。经过SD大鼠急性口服葡萄糖耐受实验,西他列汀对于降低SD大鼠OGTT峰值,推迟峰值出现有明显作用,对于降低SD大鼠OGTT曲线下面积,改善糖耐量有积极作用。结论西他列汀具有显著的降血糖,增加糖耐量的作用。相比匹格列酮,西他列汀对于ZDF大鼠的耗食量,体重没有影响,对于降低胆固醇,甘油三酯和高密度脂蛋白有作用,但不显著。对于脏器系数的改变无影响。西他列汀对于一次性口服给药处理的SD大鼠的糖耐量仍有改善作用,对于降低OGTT峰值,及曲线下面积有积极作用。
[Abstract]:Objective to test the hypoglycemic effect and effect of cilostatin on ZDF rats by using the dipeptide kininase inhibitor: cilostatin and normal SD rats, and to compare the effect of pioglitazone on the hypoglycemia of ZDF rats. The oral glucose tolerance test (OGTT) was used to test the effect of citaletine on glucose tolerance in animals. Methods male ZDF rats aged 4-6 weeks were randomly divided into three groups: solvent group and pioglitazone group. OGTT test was performed on the 15th and 25th day, and blood glucose was detected for 60 and 120 minutes. After the end of OGTT on the 25th day, the animals were euthanized, liver, kidney, epididymal fat, brown fat, soleus muscle were taken, and the liver, kidney, epididymis fat, brown fat and soleus muscle were measured. Gastrocnemius muscle, weighing and calculating organ coefficient. Blood samples were taken to determine total cholesterol, triglyceride, free fatty acids and high density lipoprotein C. fasting blood glucose was measured once a week. Daily food consumption and animal weight were measured in 40 male Sprague Dawley rats aged 6-8 weeks and adapted to the environment for at least 5 days. The postprandial blood glucose levels were measured one day before the beginning of the experiment. Animals were randomly divided into 4 groups (solvent group, cilostatin 1060mg / kg group). Then the animals fasted overnight, measured their fasting blood glucose, measured their body weight and calculated their administration. The blood glucose was measured for 120 minutes. Results ZDF rats treated with pioglitazone and cilostatin showed a significant decrease in fasting blood glucose within 6 hours. The body weight of the treatment group increased in varying degrees. However, there was no significant difference in the amount of food intake. Cholesterol, triglyceride and high density lipoprotein decreased in different degrees in the treatment group. Oral glucose tolerance test showed that, Both cilostatin and pioglitazone could improve glucose tolerance in ZDF rats. The organ coefficients of liver and kidney of ZDF rats treated with pioglitazone were significantly lower than those of other groups. Cilostatin can decrease the peak value of OGTT and delay the peak of OGTT in SD rats, decrease the area under the OGTT curve of SD rats, and improve glucose tolerance. Conclusion Cetalitin has a significant hypoglycemic effect on SD rats. Compared with pioglitazone, cilostatin had no effect on food consumption and body weight in ZDF rats, but had an effect on lowering cholesterol, triglyceride and high density lipoprotein. But it was not significant. It had no effect on the change of visceral coefficient. Cilostatin could improve the glucose tolerance of SD rats treated with single oral administration, and had a positive effect on reducing the peak value of OGTT and the area under the curve.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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