中文摘要
针对血管支架在植入过程中存在的血栓、炎症反应、内膜增生和再狭窄等并发症,项目针对性的提出构建具有抗凝、抗炎、抑制内膜增生和内皮再生等多功能的支架涂层研究策略,实现病变血管修复和治愈。基于天然内皮层持续释放的一氧化氮(NO)同时兼有以上多重功能的特点,本项目选用富含胺基的等离子体聚烯丙胺(PPAam)涂层作为支架改性平台用于共价固定3,3’-二硒代二丙酸(SeDPA),实现血液环境下原位催化释放NO。项目通过调控PPAam涂层表面胺基密度控制SeDPA接枝量,从而实现对NO催化释放速率的仿生调控。通过评价NO-催化涂层支架的NO催化活性、血液相容性以及对平滑肌细胞、内皮细胞和炎性细胞的作用行为,建立NO催化释放动力学与其生理功能之间的相关性,进一步探索NO-催化涂层支架对再狭窄及晚期血栓的综合作用行为,为基于NO催化释放的内皮功能仿生涂层应用血管支架表面改性提供理论指导和奠定技术基础。
英文摘要
Based on the recognition of the complications such as thrombus, inflammatory response, intimal hyperplasia and restenosis caused by stent intervention, a targeted strategy which can repair and cure the lesions of blood vessel was proposed. To achieve this goal, a nitric oxide (NO)-producing coating that has multiple functions such as anticoagulant, antiproliferative and anti-inflammatory properties and ability to promote re-endothelialization was presented as a vascular stent coating. The NO-producing coating was obtained by covalent conjugation of 3,3-diselenodipropionic acid (SeDPA) with glutathione peroxidase (GPx)-like catalytic activity to generate NO from S-nitrosothiols (RSNOs) via specific catalytic reaction in blood. The SeDPA was immobilized to an amine bearing plasma polymerized allylamine (PPAam) surface (SeDPA-PPAam). Here, the release rate of NO produced by the SeDPA-PPAam was adjusted and controlled by changing the amount of SeDPA on immobilized PPAam that can be accomplished through varying the density of primary amine groups of PPAam coatings. By means of evaluating the NO catalytic activity of SeDPA-PPAam, and the effects of NO produced by SeDPA-PPAam on hemocompatibility, growth behavior of endothelial cells (ECs), smooth muscle cells (SMCs) and inflammatory cells, reduction in restenosis and late stent thrombosis to understand the relationship between the NO release kinetics and physiological function, so as to provide the basic knowledge and serve as a guide for the design of the new type of the stent based on NO-functionalization.
