Genistein对动脉粥样硬化平滑肌源性泡沫细胞钾通道亚型和OX40/OX40L通路的影响及机制研究

动脉粥样硬化（AS）是心脑血管病的发病基础，严重威胁人类生命。钾通道、OX40/OX40L通路与AS的发生发展密切相关，而泡沫细胞形成是AS发生的核心。目前人们对平滑肌源性泡沫细胞认识较少，对其钾通道和OX40/OX40L通路尚无研究。我们前期的研究发现Genistein对血管平滑肌细胞钾电流有调节作用且对其亚型影响不同，然而，AS平滑肌源性泡沫细胞存在怎样的电生理特性，Genistein的作用亦是如此吗？我们通过ox-LDL诱导的平滑肌源性泡沫细胞、ApoE（-/-）小鼠模型、尸检血管及随访患者，应用膜片钳、分子生物学、免疫组化、电镜等技术，从体外到体内，从动物到人类，观察平滑肌源性泡沫细胞钾通道亚型和OX40/OX40 L通路的变化及Genistein的影响。本课题将从探索血管平滑肌源性泡沫细胞特性着手，从崭新的角度阐明AS发生的细胞、分子机制，为开发新的抗AS药物提供新思路、新靶点。

Atherosclerosis（AS）is the pathogenetic basis of cardio-cerebrovascular diseases, threatening the life of human beings. Potassium channel and OX40/OX40L pathway are closely related to AS development, in which foam cells play key role. So far, little is known about its subpopulation smooth muscle cell-derived foam cells. There is no report about potassium channel and OX40/OX40L pathway in them either. Our previous study demonstrated that Genistein regulated K+ current and potassium channel subtypes. However, what's the electrophysiological character of atherosclerotic smooth muscle cell-derived foam cells? Does Genistein work the same in these cells? To answer these questions, we will detect potassium subtype and OX40/OX40L pathway changes in smooth muscle cell-derived foam cells, and explore Genistein's effects on them in vitro and in vivo. Experimental subjects include ox-LDL-induced smooth muscle cell-derived foam cells , ApoE(-/-) deficiency mice and autopsy collection as well as follow-up patients. Main techniques in our study are patch clamp, molecular biology, immunohistochemistry, electron microscope and so on.We will explore the characteristic of smooth muscle cell-derived foam cells and clarificate cellular and molecular mechanisms of AS development from a new perspective, so as to provide a new target point and thread for new anti-AS drug development.