支架植入后血管内一氧化氮分布的变化及其对支架内血栓形成的影响

Endovascular stent implantation is an effective and widely utilized therapy for atherosclerotic stenosis, but the mechanisms of in-stent thrombus are still not clearly known. Nevertheless, it has been documented that nitric oxide (NO) play an important role in the formation of thrombus. The applicant hypothesizes that the stent-induced alteration in the mechanical environment of the host artery can affect NO concentration and disturb its distribution, hence contributing to in-stent thrombus. To verify the hypothesis, this proposed research project will carry out the following studies: (1) Develop an experimental hemodynamic system in vitro to measure the NO production rate in the stented artery. (2) Develop the artery-blood-stent interaction mechanical model after stenting; and simulate in vivo and vitro the regularity of the stent-induced alteration in local vascular mechanical environment (flow shear stress, the stress distribution in the blood vessel wall etc); based on (1), study on the distribution of NO due to the alteration of mechanical environment in the stented artery. (3) Based on the study of (2), verify if the distribution of NO in host artery would affect the platelet adhesion and activation. This study might not only provide new ideas to clarify the mechanism of in-stent thrombus, but also provide a theoretical basis for the design of new stents.

血管支架置入术是狭窄型动脉粥样硬化常见且有效的治疗手段，但是其术后血栓的发生机理至今不明。尽管如此，前人研究发现一氧化氮在血栓的形成中扮演着重要的角色。由此，申请人认为血管支架植入后力学环境变化会改变血管内一氧化氮的分布，进而影响支架内血栓的形成。为了验证该推测，本项目拟开展以下研究：（1）通过体外仿真实验技术获得支架植入血管后一氧化氮的释放规律；（2）构建在体和体外血管-血流-支架间相互作用的力学模型，探讨支架植入血管后力学环境（流动剪切应力、血管壁内应力分布等）的变化规律，并基于（1）中结果分析力学环境的改变对一氧化氮分布规律的影响；（3）研究支架植入后一氧化氮分布的改变对宿主血管内血小板粘附、活化的影响。本研究不仅能为支架内血栓形成机理提供新的研究思路，也为新型血管支架的设计提供理论依据。

支架术后的一氧化氮（NO）浓度分布规律对于支架术后宿主血管的正常功能至关重要，其功能与浓度密切相关，并受到血流动力学调整。本项目围绕NO在动脉中的传输和血流动力学进行了以下研究。1）分析支架置入对宿主血管内血流血流动力学特征影响的规律；2）分析支架术后NO等物质在宿主血管内的分布规律；3）通过体外仿真实验技术进行支架植入血管后一氧化氮的释放规律分析；4）探讨支架术后血栓形成和一氧化氮浓度之间的关系；5）开展PIV体外实验分析。本项目研究结果表明：支架置入后支架段血管出现异常血流环境，导致低水平的壁面剪切力、一氧化氮、高水平的震荡指数和相对滞留时间，这可能会加剧支架术后血栓形成的风险。本研究首次揭示了支架术后NO的分布规律及其与血流动力学特征之间的关系。本项目的成果有助于从物质传输角度揭示支架术后不良事件的发生机制，而且有助于释放NO置入体的设计和手术规划。