【作者】 白萍；

【导师】 牟振云； 张世联；

【作者基本信息】 河北医科大学 ， 流行病与卫生统计学， 2005， 硕士

【摘要】 目的:研究硒在糖尿病及其继发高血压综合症代谢紊乱中的治疗效果及可能机理,以期为评价硒对糖尿病合并高血压防治效果,选择可行的疗效评价指标提供一定的实验依据。方法:选用雄性清洁级SD 大鼠72 只,体重165±15g,适应性饲养3 天,按体重随机抽取8 只为正常组,剩余部分为造模组,禁食24h 后,造模组严格按体重一次性鼠尾静脉注射50mg/kg·bw 1%STZ(0.1mmol/L 柠檬酸缓冲液配制,PH=4.5,sigma 公司出品)造糖尿病模型,正常组大鼠给予相应体积的缓冲液鼠尾静脉注射,注射后恢复食、水,分别于3d、7d、10d 由眼眶后静脉丛取血监测血糖,以血糖≥16mmol/L 者为成糖尿病模型大鼠,未成模者再按上述程序给予二次造模。权衡体重和血糖分为5 组,其中一组8 只,为糖尿病对照组,其余组每组14 只用于造高血压模型。高血压模型采用双侧肾动脉结扎法,将肾动脉缩窄约30-50%。两周后鼠尾动脉测血压,血压大于140mmHg 的大鼠认为造模成功。实验共分6 组:Ⅰ组为正常对照组(NC 组),Ⅱ组为糖尿病对照组(DM 组),Ⅲ组为糖尿病+高血压组(DM+HP组), Ⅳ组为糖尿病+ 高血压+ 亚硒酸钠低剂量组(150μg/kg·bw),Ⅴ组为糖尿病+高血压+亚硒酸钠中剂量组(300μg/kg·bw),Ⅵ组糖尿病+高血压+亚硒酸钠高剂量组更多还原

【Abstract】 Objective: Investigate the effect and possible mechanism of selenium cure metabolism turbulence on diabetic and hypertensive rats, in order to provide some experimental basis to evaluate selenium’s prevention and therapeutic and to choose feasible estimation index. Methods: 72 healthy and cleaning male SD rats 165 ±15g were fed for 3 days to adapt to circumstances. According to body weight, 8 rats were selected randomly as normal control group (NC), the other rats were model group. After 24-hour’s fasting, the rats in model group were injected 50 mg/kg bw,1% streptozotocin sodium citrate buffer (0.1mmol/ L, pH=4.5) into tail vein to make diabetic model(DM), and the rats in NC group were injected correspond dose sodium citrate buffer into tail vein. After injection, resume to serve food and water . At the 3rd,7th and 10th day,0.4～0.6ml blood in all rats was collected from orbit venous plexus to be measured glucose. The rat whose blood glucose was more than or equal to 16.0 mmol/ L would be regarded as diabetic rat, and the same method was used to made the second model for the rat which didn’t developed diabetes mellitus. According to body weight and blood glucose, the rats were divided into 5 groups, one of them had 8 rats , which was diabetes control group. The rest rats were divided into 4 groups to made hypertension model. These rats were ligated bi-side renal artery to made hypertension model, let the renal arteries shrink 30-50% based on its original size. After two weeks, the tail artery blood pressure was measured, the rat whose blood pressure was more than or equal to 140mmHg would be regarded as success. The experiment had six groups: Ⅰnormal control group, Ⅱdiabetes control group,Ⅲdiabetes and hypertension control group(DM+HP group), Ⅳdiabetes and hypertension rats feeding low dose selenium group(150μg/kg·bw),Ⅴdiabetes and hypertension rats feeding middle dose selenium group (300μg/kg·bw), Ⅵdiabetes and hypertension rats feeding high dose selenium group (450μg/ kg·bw), selenium was supplied except selenium in ordinary feedstuff. The selenium was fed by drinking liquid. We measure once weight and thrice dose of taking food and drinking water of rats every week, and adjust concentration of supply selenium liquid based on the change of drinking water and weight of each group. Rats free eating and drinking, the supplied feedstuff is ordinary feedstuff. Supplying selenium groups was given corresponding concentration of selenium liquid. Na2SeO3 liquid were made temporarily by 100mg/L reserve liquid every day. After 4 weeks, measure the blood glucose and blood pressure once. At the end of the 8th week, all the rats were narcosised after 12-hour’s fasting, blood was withdrawn from carotid artery, resisted cruor by heparin. Blood plasma was separated fromblood timely to be kept at low temperature. Then the rats were killed, and liver, pancreas were taken out and put into 10% formaldehyde liquid for fixation and used for pathologic examination. The kidneys, odd liver, and biceps femoris of right hind legs were taken out on iced bath then washed them by cool saline, sip up by filter paper, weighed and kept at low temperature. Using the blood plasma and the saved tissue to measure these parameters: blood glucose, selenium content of blood and liver, liver starch, muscle glucose, glutamic-pyruvic transaminase, creatinine, the activity of glutathione peroxidase (GPX), malondialdehyde (MDA), the activity of ATPase , nitricoxide synthase, nitrogen monoxide, cholesterol (TC) and triglyceride(TG) , etc. Results: 1 The effect of selenium on blood glucose and blood pressure: before treatment, the blood glucose of group Ⅱ(28.89±2.14mmol/L), groupⅢ(22.5±2.25mmol/L), group Ⅳ(22.16±2.49mmol/L), groupⅤ(21.91±1.87mmol/L) and group Ⅵ(20.64±2.44mmol/L) were higher than that of groupⅠ(5.96±0.75mmol/L)( P﹤0.01); compared with group Ⅲ,Ⅳ,Ⅴ,Ⅵ,the blood glucose of group Ⅱwas higher too (P﹤0.01), there was no significant difference among the later four groups(P>0.05). At the end of experiment, blood gluc更多还原