去势诱导的雄激素缺乏小型猪肝脏胆固醇代谢的转录组学研究

项目名称： 去势诱导的雄激素缺乏小型猪肝脏胆固醇代谢的转录组学研究

项目编号： No.31200921

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 蔡兆伟

作者单位： 浙江中医药大学

项目金额： 25万元

中文摘要： 近年来雄激素与男性动脉粥样硬化之间的关系倍受人们关注，但迄今为止，低雄激素水平加速男性动脉粥样硬化形成的机理尚不十分清楚。血脂，尤其是血胆固醇水平升高是动脉粥样硬化的主要发病因素。前期我们已证实，去势诱导的雄激素缺乏导致猪脂代谢紊乱，血胆固醇水平显著升高。资料表明，肝脏是体内胆固醇代谢的最重要器官，其功能涉及胆固醇的合成、吸收和转化，与上述过程相关的肝脏酶类或受体异常均可导致血胆固醇水平升高。我们推测，低雄激素水平可能通过调控肝脏胆固醇代谢基因转录来影响血胆固醇水平。本项目建立高脂饮食诱导下，雄激素调控小型猪肝脏胆固醇代谢的动物模型，采用新一代高通量转录组测序（RNA-Seq）技术，分析去势、非去势和去势加睾酮处理小型猪肝脏转录本表达、结构及功能变化。本课题首次从转录组学角度探讨雄激素缺乏小型猪血胆固醇水平升高的分子机制，为防治低雄激素水平引起的男性动脉粥样硬化等心血管疾病提供新思路。

中文关键词： 小型猪；雄激素；高胆固醇血症；胆汁酸；动脉粥样硬化

英文摘要： In recent years, the relationship between serum testosterone levels and atherosclerosis in males attracts people's attention. However, the mechanisms of accelerated atherosclerosis in androgen deficiency males is not very clear. Serum lipids, especially elevated serum cholesterol levels is the main pathogenesis factor of atherosclerosis. In our previous research, we have confirmed that castration-induced testosterone deficiency resulted in a disorder of lipid metabolism, and serum cholesterol levels increased significantly in castrated male pigs. It is known that the liver is the most important organ for cholesterol metabolism, its function contained cholesterol synthesis, absorption and transformation. The abnormalities of liver enzyme or the receptor can lead to a higher serum cholesterol levels. We hypothesized that, the testosterone levels may affect blood cholesterol levels by regulating the expression of genes related to cholesterol metabolism in the liver. In the research, a hypercholesterolemia minature swine model were induced by castration and high-fat diet. A new generation of high-throughput transcriptome sequencing ( RNA-Seq ) technology were employed to analyze the liver transcriptome from castrated, intact and castrated plus testosterone treatment miniature pigs. This is the first time that we exp

英文关键词： Miniature pig；Androgen；Hypercholesterolemia；Bile acid；Atherosclerosis