血管内多模态X线-磁共振杂交导航/射频加热增强冠状动脉粥样硬化基因治疗的基础研究

Atherosclerotic coronary artery disease is a common and frequent-occurring disease. It seriously threaten life and living quality. Atherosclerosis is inflammation mediated chronic disease of arterial wall. Percutaneous coronary artery intervention and coronary artery bypass grafting focus on revascularization of the narrowed coronary artery. Medication therapy focuses on symptom control and myocardial infarction and death prevention. These treatment are not against the etiology atherosclerosis. Studies have proved that interleukin-10 (IL-10) is anti-inflammatory cytokine, which inhibits development of atherosclerotic plaque. In this study, a series experiments including cell experiments, rabbit femoral artery experiments, and near human sized animal with coronary artery plaque experiments will be performed under the precise navigating of XMR and tracking with T1-T2 multi-modal contrast agent (Fe3O4/Gd2O3 nano-particles) to deliver clinical applicable adeno associate virus (AAV) mediated IL-10. Meanwhile, radiofrequency hyperthermia will be employed to enhance IL-10 gene transfection and expression. The study is to develop new method to manage atherosclerotic coronary artery disease by proving the principal and providing evidence for future practice.

冠状动脉硬化性心脏病是常见病、多发病，严重威胁人类生命、影响生活质量。动脉粥样硬化是血管壁炎症介导的慢性疾病。经皮冠状动脉介入治疗术和冠状动脉旁路移植术等主要针对冠脉狭窄进行再通治疗，药物治疗主要控制症状、防止心肌梗死或死亡。上述治疗方法均未能针对病因加以施治。研究证实白介素-10（IL-10）在动脉硬化斑块内发挥抗炎作用，可抑制斑块进展。本项目拟通过一系列细胞实验、兔股动脉活体实验及近人类冠状动脉硬化的大动物实验，研究在X线/血管内磁共振（XMR）精准导航下，利用T1-T2多模态磁共振纳米造影剂（Fe3O4/Gd2O3）示踪临床适用的腺相关病毒（AAV）介导的IL-10基因投送，同时利用射频加热增强IL-10基因的转染和表达，探索治疗冠状动脉粥样硬化治疗新概念。为冠状动脉粥样硬化基因治疗的临床应用提供理论基础和实践依据。

动脉硬化性疾病严重威胁人类生命、影响生活质量。冠状动脉粥样硬化性心脏病是常见病，多发病。尽管药物治疗、介入治疗和冠脉旁路移植手术治疗的水平已有很大提高，但远期疗效仍存在很多问题。冠脉动脉硬化主要是由于炎症反应促进斑块形成。本研究利用腺相关病毒（AAV）为载体进行基因治疗，在斑块内过度表达炎症抑制因子白介素-10（IL-10），起到抑制斑块炎症的作用。研究验证了射频加热增强腺相关病毒介导的IL-10基因在血管平滑肌细胞中的表达，验证了T1-T2双模态纳米对比剂示踪病毒投送和分布，验证了射频增强IL-10抑制冠状动脉硬化斑块进展的概念。研究建立了射频加热增强炎症抑制基因治疗冠状动脉硬化的新概念，并在精准影像引导下进行了近人类大动物的基因治疗，为下一步临床研究奠定了基础。