【作者】 陈宝莹；

【导师】 魏经国； Aimin Xu；

【作者基本信息】 第四军医大学 ， 影像医学与核医学， 2006， 博士

【摘要】 肥胖与胰岛素抵抗、Ⅱ型糖尿病及心血管疾病(cardiovascular disease，CVD)的发生有密切的关系。脂肪组织可以产生多种具有生物活性的物质，称为脂肪细胞分泌因子(adipokines，ADS)。ADS参与到机体的能量代谢、炎症反应及心血管功能等病理生理过程中。肥胖时ADS的异常调节，尤其是脂联素(adiponectin，AD)、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor 1，PAI-1)及白介素6(interleukin-6，IL-6)的异常，是导致肥胖相关的胰岛素抵抗及CVD发生的重要原因。最近研究发现，肥胖可以导致机体及脂肪组织内出现氧化应激(oxidative stress，OS)。很多证据都说明，随着脂肪的快速增长，可能引起脂肪组织局部的相对低氧。这种低氧及OS对ADS表达的影响及其在肥胖相关疾病中的作用并不清楚。因此，本实验研究了低氧及OS对三种重要的ADS(AD、PAI-1及IL-6)在脂肪细胞中的调节，并探讨其可能的机制。 1 目的 (1)研究低氧对AD及PAI-1表达的调节，并对其机制进行探讨。 (2)研究OS对AD、PAI-1及IL-6表达的调节，并对其机制进行更多还原

【Abstract】 Obesity is causally associated with the development of insulin resistance, type II diabetes and cardiovascular diseases (CVD). Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of bioactive factors, named adipokines, which are involved in energy metabolism, inflammatory response and cardiovascular functions. Aberrant production of adipose-derived adipokines, especially adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1) and interleukin-6 (IL-6), is now believed to play a causative role in the development of obesity-associated insulin resistance and cardiovascular disorders. Previous study suggests that obesity may induce systemic oxidative stress (OS) and the increase of reactive oxygen species (ROS) in accumulated fat. Accumulating evidences highlight the notion that hypoxia may exist in fat depots as the fat mass increases. It is not very clear what roles the local hypoxia and OS play in the pathogenesis of obesity and obesity-related diseases. In this study, we investigated the effects of hypoxia and OS on production of three key ADS (AD, PAI-1 and IL-6), and explored the更多还原