全氟烷基化合物暴露对巨噬细胞胆固醇流出的影响研究

Exposure to perfluoroalkyl substances (PFASs) has potential effects on cholesterol metabolism as well as occurrence and development of atherosclerosis (AS) in human. The accumulation of excess cholesterol in macrophages contributes to the formation of foam cells，which is the hallmark of the atherosclerotic lesion. Cholesterol efflux plays an important role in regulating cellular cholesterol. However, there isn’t any study about the exact effect of PFASs exposure on cholesterol efflux. The present study will recruit young adults from different urban and rural regions, analyze how PFASs exposure will impact the human serum mediated cholesterol efflux of THP-1 macrophages, and effects of PFASs exposure on key genes in the pathway, such as ABCA1, ABCG1, ACAT, NCEH, HMGCR, NPC1, PPAR, LXR and apoA-I will be discussed. Then in vitro study will be conducted in order to find out effects of PFASs exposure on the high density lipoprotein (HDL) mediated cholesterol efflux and relevant key genes. The implementation of this project will help to reveal the effect of PFASs exposure on cholesterol efflux in macrophages and its mechanism, and provide a new experimental basis for the further understanding of the effect of PFASs on cholesterol metabolism and AS development.

全氟烷基化合物（PFASs）暴露对人体胆固醇代谢和动脉粥样硬化（AS）的发生发展存在潜在影响。胆固醇在巨噬细胞中过量聚集形成泡沫细胞是AS的关键病理事件，胆固醇流出对调节细胞内胆固醇水平起重要作用，然而PFASs暴露对胆固醇流出功能的影响研究尚属空白。本项目首先选取城乡不同地区的青年人为研究对象，分析PFASs暴露对人血清介导THP-1巨噬细胞胆固醇流出功能的影响，并分析其对巨噬细胞胆固醇流出通路中关键蛋白ABCA1、ABCG1、ACAT、NCEH、HMGCR、NPC1、PPARs、LXRs及apoA-I的调节作用；然后进行离体试验，观察PFASs暴露对高密度脂蛋白（HDL）介导的胆固醇流出功能及其关键蛋白的影响。本项目的实施将有助于揭示PFASs暴露对巨噬细胞胆固醇流出功能的影响及其机制，为深入了解PFASs对胆固醇代谢和AS发生发展的影响提供新的实验依据。