胰岛素抵抗大鼠外周血白细胞胰岛素信号转导分子mRNA的表达及氨基胍的保护机制

发布时间：2018-02-05 00:52

本文关键词： 胰岛素抵抗胰岛素受体一氧化氮诱导型-氧化氮合酶氨基胍　出处：《山东大学》2005年硕士论文　论文类型：学位论文

【摘要】：目的:以外周血白细胞作为靶细胞,检测高糖饮食诱导的胰岛素抵抗大鼠及加用氨基胍治疗大鼠胰岛素信号转导通路关键分子mRNA及诱导型一氧化氮合酶mRNA(iNOS mRNA)的表达,并通过血生化指标的检测,从基因转录水平上探讨胰岛素抵抗的发病机制和氨基胍的保护作用机制。方法:将Wistar大鼠随机分为正常对照组、高糖对照组以及高糖加氨基胍(AG)治疗组,饲养6个月,每月断尾取血,用本室设计的优化原位杂交技术测定外周血白细胞iNOS mRNA、胰岛素受体mRNA(IR mRNA)、磷脂酰肌醇3-激酶P85 α亚单位mRNA(PI-3K P85 α亚单位mRNA)、蛋白激酶B α mRNA(PKB α mRNA)、蛋白激酶B β mRNA(PKB β mRNA)及葡萄糖转运蛋白2mRNA(GLUT2 mRNA)的表达情况。每月测定空腹血浆血糖、胰岛素、糖化血清蛋白(GSP)及一氧化氮(NO)含量。比较各组血生化指标、外周血白细胞iNOS mRNA以及胰岛素信号转导通路分子mRNA表达水平的差异。结果:高糖对照组血糖、血浆胰岛素、GSP及NO水平高于正常对照组,胰岛素敏感指数低于正常对照组;外周血白细胞iNOS mRNA和PKB α mRNA表达水平高于正常对照组,IR mRNA、PI-3K P85 α亚单位mRNA、PKB β mRNA表达水平低于正常对照组,GLUT2 mRNA表达水平无变化。 AG治疗组血生化指标及外周血白细胞信号分子mRNA的表达与高糖对照组具有相同的变化趋势。但随着AG治疗时间的延长,与高糖对照组相比,2月后,血浆NO水平降低,外周血白细胞IR mRNA表达水平升高;5月后,血糖、血浆GSP较高糖对照组降低,外周血白细胞iNOS mRNA,PKB α mRNA表达水平降低,且后者恢复至正常水平,PI-3K P85 α亚单位mRNA、PKB β mRNA表达水平升高,且前者于6月时恢复至正常水平,胰岛素敏感指数于6月时升高;两组各月血浆胰岛素水平与外周血白细胞GLUT2 mRNA表达水平无显著差异。
[Abstract]:Objective: to use peripheral white blood cells as target cells. The insulin resistance rats induced by high glucose diet and the rats treated with aminoguanidine were detected. The key molecules of insulin signal transduction pathway (mRNA) and inducible nitric oxide synthase (mRNA(iNOS) mRNAs were detected. The expression of. The pathogenesis of insulin resistance and the protective mechanism of aminoguanidine were discussed from the level of gene transcription. Methods: Wistar rats were randomly divided into normal control group, high glucose control group and high sugar plus aminoguanidine group. The iNOS mRNAs and insulin receptor mRNA(IR mRNAs in peripheral blood leukocytes were determined by the optimized in situ hybridization technique designed by our laboratory. Phosphatidylinositol 3-kinase P85 伪 subunit mRNA(PI-3K P85 伪 subunit mRNAs, protein kinase B 伪 mRNA(PKB 伪 mRNAs. The expression of protein kinase B 尾 mRNA(PKB 尾 mRNAand glucose transporter 2mRNA-GLUT2 mRNA. fasting plasma glucose and insulin were measured monthly. The contents of glycosylated serum protein (GSPs) and nitric oxide (no) were compared in each group. The expression levels of iNOS mRNA and insulin signal transduction pathway (mRNA) in peripheral blood leukocytes were different. Results: the levels of blood glucose, plasma insulin GSP and no in the hyperglycemic control group were higher than those in the normal control group, and the insulin sensitivity index was lower than that in the normal control group. The expression levels of iNOS mRNA and PKB 伪 mRNA in peripheral blood leukocytes were higher than those in control group. The expression of PI-3K P85 伪 subunit mRNA was higher than that of normal controls. The expression level of PKB 尾 mRNA was lower than that of control group. There was no change in GLUT2 mRNA expression. The changes of serum biochemical indexes and the expression of mRNA in peripheral blood leukocytes in AG treatment group were similar to those in high glucose control group, but with the prolongation of AG treatment time, it was compared with high glucose control group. After February, the level of plasma no decreased and the expression of IR mRNA in peripheral blood leukocytes increased. After May, blood glucose and plasma GSP were lower than those of high glucose control group, and the expression of iNOS mRNA-PKB 伪 mRNA in peripheral white blood cells was decreased, and the latter returned to normal level. The expression of PI-3K P85 伪 subunit mRNA-PKB 尾 mRNA increased, and the former returned to normal level on June, and the insulin sensitivity index increased on June. There was no significant difference between the level of plasma insulin and the expression of GLUT2 mRNA in peripheral blood leukocytes between the two groups.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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