【作者】 凌宏艳；

【导师】 胡弼；

【作者基本信息】 南华大学 ， 药理学， 2005， 硕士

【摘要】 目的 探讨罗格列酮（RSG）对胰岛素抵抗（IR）大鼠主动脉内皮功能的保护作用及其可能机制。 方法 采用高果糖饲料喂养SD大鼠4周制备IR大鼠模型,通过以下指标的检测判断模型是否成功:在实验的第0、2、4、6、8周末大鼠空腹过夜,测定收缩压后,取尾部血样测定空腹血糖、血胰岛素并计算胰岛素敏感指数的变化。以普通饲料喂养作为正常对照组,4周后分别用与不用罗格列酮(5mg.Kg^-1.d^-1,溶于饮水中灌胃)处理对照组和IR组,持续4周。8周末通过腹腔注射葡萄糖耐量试验（IPGTT）、胰岛素敏感指数的变化和胰腺组织HE染色来分析胰岛β细胞功能变化。随后采用血管坏灌流方法,观察各实验组动物离体胸主动脉坏对新福林（PE）、氯化钾（KCl）的收缩反应和对乙酰胆碱（ACh）、硝普钠（SNP）的舒张反应;以及用一氧化氮合酶（NOS）的抑制剂N-硝基-L-精氨酸甲酯（L-NAME）预孵育血管30min后主动脉环对hCh的舒张反应。为探讨其机制,取8周末空腹血测定血脂、血清一氧化氮（NO）、丙二醛（MDA）、超氧化物岐化酶（SOD）、细胞间粘附分子-1（ICAM-1）、血管粘附分子-1（VCAM-1）和血浆内皮素（ET₁）的含量及主动脉一氧化氮合酶的活性、MDA含量、SOD的活力和ICAM-1、VCAM-1的表达。更多还原

【Abstract】 Aims To investigate the protective effect of rosiglitazone （RSG） on aortic endothelial function of insulin resistant （IR） rats and the underlying mechanism.Methods Male SD rats were fed with high fructose diet for 4 weeks to induce IRrats model. To verify IR rats model, the following indexes were measured respectively in each group: Systolic blood pressure （SBP） were measured after fasting overnight, subsequently, blood samples were withdrawn from the end of tails of animals for fasting blood glucose （FBG）, fasting serum insulin （FSI） at the end of weeks 0 ,2,4,6,8. and insulin sensitive index （ISI） were calculated. Control group rats were fed with common diet. After 4 weeks, rats were treated with or without rosiglitazone (5mg.Kg^-1.d¹ dissolved in water) for 4 weeks., At the end of 8th week, intraperitoneoclysis glucose tolerance test （IPGTT） insulin sensitive index （ISI） and morphology of pancreas were taken to evaluate pancreatic 3 cell function. At last, the vascular function test was performed. The thoracic aortic ring of SD rats was mounted on a bath system, The effect of rosiglitazone on the contraction elicited by L-phenylephrine （PE） and potassium chloride （KCl） and the relaxation induced by acetylcholine （ACh） and sodium nitroprusside （SNP） were measured. To explore the mechanism , nitric oxide synthase （NOS） inhibitor N^ω-nitro-L-arginine methyl ester （L-NAME） was used. At the same time, Blood lipid, NO, MDA, SOD, ICAM-1, VCAM-1, ET-1 levies; thoacic aortic nitric oxide synthase （NOS ） activity , MDA content, SOD activity and aortic expression of ICAM-1, VCAM-1 were measured respectively in groups.更多还原