【作者】 周寿红；

【导师】 胡弼；

【作者基本信息】 南华大学 ， 药理学， 2005， 硕士

【摘要】 目的:研究17-β-雌二醇对高果糖诱导的去卵巢大鼠胰岛素抵抗的抑制作用及其可能机制。 方法:1.建立高果糖诱导的去卵巢胰岛素抵抗大鼠模型,生理剂量（30μg/Kg.d）17-β-雌二醇进行替代;2.动态监测体重、收缩压、血糖、血清胰岛素和胰岛素敏感指数;3.测定血清中TG、TC、LDL、HDL、E₂、NO的水平;4.注射糖耐量试验检测胰岛素敏感性和胰岛β细胞功能;5.胰腺HE染色观察胰岛的结构;6.离体血管环灌流实验检测主动脉内皮功能;7.免疫组织化学技术检测骨骼肌胰岛素受体α和葡萄糖转运体4的表达。 结果:1.与卵巢切除组（OVX）或果糖喂养组（F）相比,卵巢切除+高果糖喂养组大鼠体重显著性增加（P<0.05）,收缩压显著性升高（P<0.05）,血清甘油三脂、总胆固醇、低密度脂蛋白胆固醇、空腹血糖均显著性升高（均P<0.05）,空腹血清胰岛素极显著性升高（P<0.01）,高密度脂蛋白胆固醇显著性降低（P<0.05）,胰岛素敏感指数显著性降低（P<0.05）,葡萄糖耐量显著性减低（P<0.05）,胰岛β细胞受损;17-β-雌二醇替代组逆转上述变化。2.与卵巢切除组（OVX）或果糖喂养组（F）相比,卵巢切除+高果糖喂养组大鼠骨骼肌胰岛素受体α和葡萄糖转运体4表达降低,17-α-雌二醇替代后能增加其表达。3.卵巢切除+果糖喂养组大鼠（OVX+F）与卵巢切除组（OVX）或果糖喂养组（F）相比,血清NO显著性降低,胸主动脉对PE的收缩反应显著性增强,对Ach的舒张反应显著性降低,17-β-E₂能逆转上述改变,L-NAME可部分的阻断17-β-E₂增强去卵巢胰岛素抵抗大鼠胸主动脉对Ach的舒张反应的作用;各组大鼠胸主动脉对SNP的舒张反应无显著性差异;各组大鼠胸主动脉去内皮后对PE的收缩反应无显著性更多还原

【Abstract】 Aim To investigate the inhibiting effect and mechanisms of 17- β-estradiol on insulin resistance induced by the high fructose diet in ovariectomized rats .Methods The ovariectomized mature female Sprague - Dawley(S-D) rats were fed with the high fructose diet for eight weeks to induce insulin resistance. The physiological-dose 17-β -E2 (30μ g/Kg. d)was injected subcutaneously every day. Body weight (BW) and systolic blood pressure (SBP) were measured every week. Fasting blood suger(FBS), fasting serum insulin(FSI) and insulin sensitivity index(ISI)were measured every two weeks. Glucose tolerance, plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol(LDL-C) were measured. The morphology of pancreas were analysed by HE. The vascular functions test was performed by using isolated blood vessel method. The contractive response of thoracic aorta rings induced by L-phenylephrine (PE) and the relaxative response of thoracic aorta rings induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. Nitric oxide synthase (NOS) inhibitor :N-nitrio-L-argine methyl ester (L-NAME) was used. The expression of insulin receptor α and glucose transporter 4 in skeletal muscle were measured by immunohistochemistry.Results Compared with the ovariectomized group ( OVX) or fructose fedgroup(F), BW (P<0. 05), SBP (P<0. 05), the levels of plasma TG, TC, LDL-C and FBS (all P<0. 05), FSI(P<0. 01) were increased significantly,the plasma HDL-C level and ISI were decreased significantly (respectly, P<0. 05, P<0. 05), glucose tolerance was decreased significantly (P<0. 05), injury of pancreatic P-cells was observed in the ovariectomized + fructose fed group. These effects were更多还原