PVAT功能改变对骨桥蛋白表达的影响在糖尿病血管内膜增生中的作用及其机制研究

项目名称： PVAT功能改变对骨桥蛋白表达的影响在糖尿病血管内膜增生中的作用及其机制研究

项目编号： No.81470585

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： 刘昌伟

作者单位： 中国医学科学院北京协和医院

项目金额： 70万元

中文摘要： 糖尿病患者血管成形术后内膜增生的严重程度明显高于非糖尿病患者，其具体机制尚不明确。最近研究显示，高血糖除直接导致血管内膜损伤外，还可造成血管周围脂肪组织（PVAT）的功能异常，导致其脂肪因子与炎性介质分泌失衡。此外，骨桥蛋白（OPN）可促进损伤后血管平滑肌细胞及外膜细胞的迁移，被认为是血管损伤修复过程中重要的始动因素。本研究拟通过体外实验明确高血糖对脂肪细胞、巨噬细胞内分泌及炎性功能的影响以及上述改变对血管内皮细胞OPN表达及内皮细胞功能的影响，进而通过体内动物实验明确糖尿病可否通过改变PVAT内分泌功能而影响血管壁内OPN表达及加重内膜增生的程度，并探讨其分子生物学机制。上述研究结果可能为探究糖尿病血管病变的机制以及减轻血管损伤后内膜增生提供新的思路及治疗靶点。

中文关键词： 下肢动脉硬化闭塞症；2型糖尿病；骨桥蛋白；血管周脂肪组织；内膜增生

英文摘要： The degree of neointimal hyperplasia after vascular injury inpatients with diabetes is heavier than the patients without diabetes. The specific mechanisms are under exploring. Latest studies shows that high glucose not only directly causes the injury of vascular endothelium, but also leads to the dysfunction of perivascular adipose tissue (PVAT) through break out the balances of adipokines and inflammative factors. In addition, osteopontin (OPN) is regarded as one of the initial factors during vascular repair after injury through promotes the immigration of vascular smooth muscle cells and adiventitia cells. Whether PVAT in high glucose condition can impact on the level of neointimal hyperplasia through changing the expression of OPN or not is not clear. In this study, we plan to verify if high glucose can affect the endocrimal fuctions of adipose cells and inflammative functions of macrophagesin vitro and in vivo and we expect to find out if these changes can impact on the expression of OPN in vascular endothelial cells (ECs) and the function of ECs. Furthermore, we will explore the molecular mechanisms in these processes. The results of this study will provide new ideas on the mechanism of high glucose enhance the level of vascular lesions and help to explore new therapy targets of preventing neointimal hyperplasia after vascular injury.

英文关键词： Peripheral artery occlusive disease;Type 2 diabetes;Osteopontin;Perivascular adipose tissue;Intimal hyperplasia