亚砷酸钠对血管内皮祖细胞修复能力的效应及其分子机制研究

项目名称： 亚砷酸钠对血管内皮祖细胞修复能力的效应及其分子机制研究

项目编号： No.21277057

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 环境科学、安全科学

项目作者： 李荣贵

作者单位： 吉林大学

项目金额： 80万元

中文摘要： 我们的前期研究表明亚砷酸钠①引起的血管内皮细胞凋亡在地方性砷中毒周围血管损伤中起重要作用；②通过抑制内皮细胞的迁移和增殖而破坏其对损伤血管的修复功能；③明显的改变了血管内皮细胞的microRNA 表达谱。这一结果揭示了砷化物引起的血管损伤经久不愈的细胞学和分子基础。最近研究发现骨髓细胞中存在着一类血管内皮祖细胞(EPCs， endothelial progenitor cells)， 具有极强的增殖潜能，可分化为成熟的内皮细胞，通过血液循环迁移并定居在受损伤血管的内皮细胞层，分化为成熟的内皮细胞对损伤的血管进行修复。业已证明EPCs在维护血管完整性及促进损伤血管的修复和再建过程起关键作用。然而关于砷化物对EPCs的血管损伤修复功能作用的研究尚未见报道。本项目拟应用体内、外实验模型研究亚砷酸钠对EPCs迁移、增殖、分化效应的分子机理，进一步为砷化物血管损伤的发病机制提供新依据。

中文关键词： 环境砷暴露；血管损伤；生物效应；血管内皮祖细胞；生物反应器–微载体

英文摘要： Our previous studies indicated ① that arsenic-induced apoptosis of endothelial cells might play a crucial role in arsenic induced vascular injury; and ② that cell migration and proliferation which are required for the endothelial cell to repair the damaged blood vessels, were inhibited;③altered expression profile of microRNA. These results reveal the cytological and molecular basis for the arsenite-induced vascular injury. Recent studies show that in bone marrow there is existence of endothelial progenitor cells (EPCs) that has a strong proliferate potential and could migrate through the blood circulation, differentiate into mature endothelial cells and settle in the injured vascular endothelial cells layer to repair the damaged blood vessels. It has been proven that EPCs play a key role in the maintenance of vascular integrity and reparation of damaged blood vessels. However studies on arsenite effect on EPCs has not been reported. The project intends to carry out in vivo and in vitro studies on the effects of arsenite on the migration, proliferation and differentiation of EPCs and its underlying mechanism. The results would provide a new light on the mechanism by which arsenite damage the blood vessel.

英文关键词： Environmental arsenic exposure；Vascular injury；Biological effects；Endothelial progenitor cells；Bioreactor micro-carrier cell culture system