项目名称： UCMSCs抑制IFN-I分泌调节EPCs功能治疗狼疮早发动脉粥样硬化的机制研究

项目编号： No.81471533

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王世颖

作者单位： 南京大学

项目金额： 80万元

中文摘要： 动脉粥样硬化(AS)在系统性红斑狼疮(SLE)早期即可发生，已成为狼疮患者重要死因，传统治疗效果不佳。脐带间充质干细胞(UCMSCs)是治疗难治性SLE的一项新技术，机制包括抑制I型干扰素（IFN-I）分泌等。研究发现MSCs亦可通过抑制炎症反应治疗apoE-/- AS模型鼠，但其对狼疮患者早发AS作用尚未可知。前期我们证实gld.apoE-/-狼疮早发AS模型鼠体内IFN-I表达过多，影响内皮祖细胞(EPCs)数量及功能，引发其AS发病。在本项目中，我们将检测UCMSCs移植治疗对gld.apoE-/-鼠早发AS影响，并探讨其可能的作用机制，为狼疮患者早发AS发展新的治疗方案提供理论依据。

中文关键词： 系统性红斑狼疮；动脉粥样硬化；间充质干细胞；I型干扰素；内皮祖细胞

英文摘要： Premature atherosclerosis (AS) is an important cause of death in patients with systemic lupus erythematosus (SLE) with poor traditional treatment. Umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a new technology for refractory SLE treatment through inhibiting secretion of type I interferon (IFN-I) and so on. Studies found that MSCs improved AS in apoE-/- mice model, but the role of MSCs in lupus patients with premature AS remains unclear. We previously confirmed IFN-I pathway over-secretion induced the depletion and dysfunction of EPCs, thus might contribute to the development of premature AS in gld.apoE-/- mice. In this project, we will detect the effect of UCMSCs transplantation therapy for premature AS in gld.apoE-/- mice, and to explore its possible mechanisms to provide a theoretical basis for new treatment options for premature AS development in SLE patients.

英文关键词： systemic lupus erythematosus;atherosclerosis;mesenchymal stem cells;type I interferon;endothelial progenitor cells