金纳米颗粒涂层支架光热效应预防大鼠气道支架植入后支架相关狭窄的实验研究

Benign and malignant central airway obstructions can lead to debilitating symptoms (e.g., dyspnea, asthma and chest tightness) and can be a life-threatening condition. As a minimally invasive alternative to surgery, airway stenting has been increasingly used for the treatment of tracheal and bronchial obstructions secondary to various causes. However, after the airway stents were inserted for a certain period of time, granulation tissue formation occurs through the stent meshes thereby causing stent-related stenosis. This has been considered to be a major limitation of airway stenting. Although covered and drug-eluting stent have been introduced to prevent stent-related stenosis, long-term patency remains to be similarly poor. .With plasma resonance and photothermal reaction characteristics, gold nanoparticle (GNP) can generate significant photothermal effect. In addition, it could be coated to the surface of stents by polydopamine (PDA) coating method. This study aims to investigate the feasibility, safety and effectiveness of gold nanoparticle-coated stents (GNP-coated stent) in preventing stent-related stenosis after implantation in the rat's trachea by inducing apoptosis and inhibiting cell proliferation with photothermal effect. Furthermore, the possible mechanisms involved (e.g., cellular proliferation and apoptosis) of GNP-coated stent for preventing are also investigated in this study.

良、恶性中心气道狭窄常导致患者呼吸困难、气喘或胸闷，严重时可危及生命。气道支架植入术作为一种新兴的微创治疗手段，已广泛用于各种病因所致的气管、支气管狭窄的治疗。然而，现有气道支架仍存在一定缺陷——在支架植入一定时间后，可导致支架区域肉芽组织增生，进而引起支架相关狭窄的发生。现有支架狭窄防治技术（如覆膜、药物涂层等）仍无法解决支架两端狭窄及术后长期通畅问题。.金纳米颗粒（gold nanoparticle,GNP）具有等离子共振和光热效应特性，在近红外光激发下，GNP可产生显著的热杀伤作用。此外，通过聚多巴胺涂层技术，可将GNP稳定地涂层于支架表面并表现出上述效应。本研究拟利用GNP涂层支架热杀伤效应，探究其在预防或抑制大鼠气道支架植入后相关狭窄发生的可行性、安全性和有效性，进而阐明其可能涉及的凋亡、增殖等相关机制，为临床提供一种针对支架相关狭窄发生的新型防治手段。

良、恶性疾病引起的气道狭窄是影响患者健康的重要问题之一。气管支架植入术作为一种新兴的微创治疗手段，已广泛用于各种原因所致的气管狭窄的治疗，然而支架相关狭窄是限制支架长期通畅性和治疗效果的重要问题，如何减少支架相关狭窄，提高气管支架的治疗效果是临床亟需解决的重要问题之一。纳米技术是新型的、具有潜力的新技术，其在医学技术革新中具有重要地位，已广泛用于医学诊断及治疗的新方法和新器械及药物的研发。因此，基于气管支架的相关临床问题及金纳米颗粒的理论及技术优势，本项目拟探索性制备金纳米颗粒（AuNPs）涂层支架，以期其可成为有效解决气管支架植入后支架相关狭窄的临床问题的新选择。研究采用物理法成功制备了AuNPs涂层支架，且通过体内外实验验证其具有良好的光-热效应。接着，通过大鼠气管支架植入实验发现单一AuNPs涂层支架较非纳米涂层对照支架减少支架相关狭窄的发生，而AuNPs涂层支架联NIR治疗可通过产生光-热效应有效减少狭窄的发生，且AuNPs涂层支架联NIR治疗未显著损伤肝肾功能或引起肺部炎症，提示AuNPs涂层支架介导的光-热效应具有良好的有效性及安全性。同时，实验发现AuNPs涂层支架联NIR治疗较单一AuNPs涂层支架及对照支架有效减少局部气管组织的炎性反应，提示其可能是相关疗效机制之一。综上，本研究发现验证了AuNPs涂层支架制备的技术及方法的可行性，并为AuNPs涂层支架用于预防气管支架植入后支架相关狭窄的转化应用提供了初步的理论依据。