炎症反应参与主动脉夹层腔内治疗后血管重构的机制及干预策略研究

Aortic dissection is one of the extremely dangerous cardiovascular diseases. Endovascular treatment has been widely used because of its minimal invasion and effectiveness. However, the adverse events including stent graft-induced new entry could seriously influence the prognosis of patients with aortic dissections, which remain to be solved urgently. Our recent study revealed that the Systemic and local inflammation after the endovascular treatment were closely related to the occurrence of adverse events. And combined treatment with anti-inflammatory drug could promote vascular repair..Then, what is the time-dependent effect and characteristics of the inflammation involved in aortic remodeling after endovascular treatment? Could the novel designed drug-carried stent-graft regulate the inflammation, and reduce the related adverse events through affecting the process of aortic remodeling?.In the project, we plan to establish a condition-optimized risk prediction model by prospective clinical study, and explore the relationship between the postoperative inflammation and the adverse events..Second, in the animal model of endovascularly-treated aortic dissections, we would study the time-dependent characteristics of inflammation and its effect on biomechanical properties of vascular wall, by linkage analyses of imaging data (e.g. CTA, PET-CT) and examinations of biological samples (inflammatory mediator of circulatory blood including IL-6, TNF-α etc; Histopathology and the biomechanical index of the aortic tissues including elastic modulus, tensile breaking point etc)..Third, with the newly designed glucocorticoids-loaded super-flexible stent-graft, we would regulate the inflammation process, and investigate the role of inflammation in aortic homestasis and vascular remodeling..The project might raise new targets and strategies for diagnosis and treatment of aortic diseases, and provide new insight into inflammation-involved vascular remodeling.

主动脉夹层病情凶险，腔内治疗因微创有效而广为应用，但术后再发破裂等不良事件严重影响预后，亟待研究。我们新近研究发现：腔内治疗后主动脉管壁存在炎症反应，且与不良事件发生密切相关，而联合抗炎治疗可促进血管修复。那么腔内治疗后炎症反应调控血管重构的时程效应特征是怎样的？能否构建新型载药腔内移植物干预炎症，调控主动脉重构过程，减少不良事件发生？本项目拟：①通过前瞻性临床研究建立优化条件的风险预测模型，探讨主动脉夹层腔内治疗后炎症反应与不良事件发生的对应关系；②在主动脉腔内治疗动物模型上，结合影像学（CTA、PET-CT等）指标和生物样本检测，分析炎症反应的时相特征及其对管壁生物力学性质的影响；③利用近期研发的新型载糖皮质激素超柔顺腔内移植物干预炎症，研究炎症调控主动脉稳态进而影响血管重构转归的效应和机制。本项目将为主动脉疾病的诊治提供新的靶标和策略，为研究炎症参与的主动脉血管重构过程提供新思路。

1.研究背景：.主动脉夹层病情凶险，腔内治疗因微创有效而广为应用，但术后再发破裂等不良事件严重影响预后，亟待研究。我们新近研究发现：腔内治疗后主动脉管壁存在炎症反应，且与不良事件发生密切相关，而联合抗炎治疗可促进血管修复。那么腔内治疗后炎症反应调控血管重构的时程效应特征是怎样的？能否构建新型载药腔内移植物干预炎症，调控主动脉重构过程？ .2.主要研究结果：.通过临床研究，我们发现：主动脉夹层腔内治疗后存在白细胞计数、体温、心率、CRP、TNF-α及IL-6峰值变化为特征的全身炎症反应，且程度与腔内治疗不良预后有关，CRP是可能的预测因子之一；术后小剂量糖皮质激素全身干预可以抑制腔内治疗后炎症指标的升高，促进体温、心率等生命体征的恢复和疼痛症状的缓解，但对全因死亡、心脑血管事件及逆撕夹层等主动脉不良事件发生率未见明显影响,亦未见对假腔血栓化等血管重塑的明显影响。.我们认为上述结果可能是因为全身给予的小剂量糖皮质激素（尽量减少可能的毒副反应）在管壁炎症局部（特别是与移植物接触部位）难以达到有效浓度。进而，我们设计了附载甲强龙的新型主动脉腔内移植物系统。基于腔内治疗术后炎症反应时程特点，我们采用“三明治”同轴电纺丝法构建可控释载药覆膜，性能达到预期要求。.我们在大动物主动脉夹层模型上，成功应用了该新型载糖皮质激素主动脉移植物，基于组织病理、血液学、影像学（PET/CT等）的检测分析表明，该新型主动脉移植物能明显抑制巨噬细胞等炎细胞在管壁中的聚集，降低全身炎症反应，有效促进局部管壁的修复重塑。.3. 科学意义：.本项目所获结果将为主动脉疾病的诊治提供新的靶标和策略，为研究炎症参与的主动脉血管重构过程提供新思路。