慢病毒介导siRNA靶向干扰PLTP表达对胆固醇逆向转运的作用

项目名称： 慢病毒介导siRNA靶向干扰PLTP表达对胆固醇逆向转运的作用

项目编号： No.31300648

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 田丽

作者单位： 四川大学

项目金额： 22万元

中文摘要： 磷脂转运蛋白(PLTP)作为脂质转运家族的一员，不但在脂蛋白代谢中起调控作用，还调节胆固醇的代谢。PLTP缺陷和PLTP转基因小鼠介导较少的巨噬细胞的胆固醇流出，但高密度脂蛋白(HDL)浓度差异调整(与野生型相比PLTP转基因和缺陷小鼠有显著的降低HDL水平)后与野生型小鼠相同的水平，这种差异就不存在了。PLTP在胆固醇逆向转运(RCT)中发挥何种作用(促进或抑制)？答案仍然不是很明确。我们推测，其可能涉及与动脉粥样硬化(AS)有关的HDL代谢和功能的变化。本项目拟通过：①筛选高效沉默PLTP表达的siRNA，构建表达siRNA的重组载体并进行慢病毒包装；②在整体动物和细胞水平，探讨siRNA下调PLTP表达，HDL亚类分布、RCT、RCT相关因子及动脉病变的变化。本研究将明确PLTP表达变化与RCT之间的关系，对于PLTP作为防治AS的新靶标提供新的依据。

中文关键词： 磷脂转运蛋白；动脉粥样硬化；胆固醇逆向转运；高密度脂蛋白亚类颗粒；小干扰RNA

英文摘要： phospholipids transfer protein(PLTP) belongs to a family of lipid transfer protein. It has not only mediates lipoproteins metabolism and also modulates the transfer of cholesterol. The study have shown that both PLTP-deficient and PLTP-transgenic mouse plasma mediates less macrophage cholesterol efflux, but after adjusting for differences in high density lipoprotein(HDL) cholesterol concentration (both PLTP-transgenic and deficient mice have significantly lower HDL cholesterol levels than wild-type mice) to the same levels as wild-type mouse plasma, this difference was negated. The role of PLTP in reverse cholesterol transport(RCT) is still not clear (promote or inhibit). We speculated that may involve its impact on HDL remodelling and function. We intend to:①screen siRNA of high efficiency to stable silence PLTP gene expression, construct the recombinant vector and lentiviral packaging;② investigate the effect of specific siRNA interference of PLTP gene expression on HDL subclasses distribution, RCT, RCT related factors, along with arterial lesions in vivo and vitro. Based on the above mentioned, it is possible for us to clarify the relationship between PLTP expression and RCT，to provided the new evidence with PLTP as a new target in the prevention and treatment of atherosclerosis(AS).

英文关键词： Phospholipids transfer protein；Atherosclerosis；Reverse cholesterol transport；High density lipoprotein subclass particle；Small interfering RNA