动脉粥样硬化斑块热物理治疗的基础研究

Atherosclerosis is the major cause of the first killing diseases of human being. But current treatment modalities focuses on destroy all the abnormally proliferated vascular smooth muscle cells, and can't spare the adjacent endothelial layer which results in deficiency of vascular long term patency rate. More than 50% patient may have restenosis 1- 2 years after treatment. However, the most recent studies have shown that it is the multipotent vascular stem cells and the activated SMCs that have caused the hardening of the arteries. Thus only the stemness of the multipotent vascular stem cells and the proliferation function of the activated SMCs are the treatment target. Therefore, we propose a new therapy for atherosclerosis, RF mediated hyperthermia. Through molecular thermal damage mechanisms study, especially mechanisms study of the response the stemness of the multipotent vascular stem cells and proliferation ability of the activated SMCs to temperature from both theoretical and experimental point of view, a workable treatment modality will be found. Besides, by using the penetrating heating effect of Radio Frequency (RF) coupled with surface cooling function, heating can be focused on the abnormally proliferating smooth muscle cells while spare the endodermis. By analysis of the complex mechanism of heat transfer during the treatment, combining with thermal sensitivity of the abnormally proliferated smooth muscle cells and experiments with isolated tissue and associated animals, a variety of factors influencing the therapeutic processes, including the surface cooling factor of different RF balloon, the power of RF heating, the morphology of lesion tissues, the blood flow rate and the vascular deformation degree, will be studied. And a radiofrequency based hyperthermia balloon for atherosclerosis treatment will be developed and effective treatment strategies for different degree of atherosclerosis will be designed.

动脉粥样硬化是心脑血管疾病的主要成因，已有的治疗方法包括热物理治疗在杀灭所有病变组织的同时对血管内皮层造成严重损伤，治疗后血管远期通畅率不够，血管常发生再狭窄等问题。而最新的研究发现是由硬化血管斑块中存在的少数多功能血管干细胞，在刺激后形成激活的平滑肌细胞快速增殖引起了血管的硬化。因此项目提出将多功能血管干细胞干性、激活的平滑肌细胞快速增殖能力，作为热物理治疗的靶点，通过不同细胞与热物理作用分子响应机制的实验和理论研究，找到对这些细胞选择性杀伤、同时保护内皮层的热物理作用程序；再接着利用射频的穿透加热作用联合表面冷却功能，发展新的治疗技术，使得加热作用穿越内皮层选择性作用在平滑肌增生部位；最后项目还将研究射频球囊表面冷却条件、射频加热功率和程序、病变组织结构、血管中血流以及血管变形等对传热的影响机制，从理论的角度分析获得治疗过程精确控温的方法。

针对目前动脉粥样硬化治疗术后再狭窄这一难点，基于热物理作用的优越性，项目提出了利用温热的方法与球囊成形术相结合的新治疗方法，针对发展该治疗方法与仪器所需的热物理作用与血管斑块作用机理，在血管这一特殊组织中的热量产生，传输机制以及重要影响参数作用规律，可能的安全性和有效性等关键科学问题，着重探索了血管平滑肌细胞和多潜能血管干细胞对温度的敏感性，结果提示温热对于可以杀灭增殖的平滑肌细胞同时抑制多潜能血管干细胞的分化能力，项目成功构建了热电力三场耦合的模型，研究了各物理量变化规律，研究结果发现通过电极的特殊控制，可以实现不同形态动脉粥样硬化斑块的加热，产生温热的作用，特别是通过热物理作用与球囊打开的时间窗口，可以将传统球囊成形术中的应力大大降低。项目同时完成了动脉粥样硬化射频热物理治疗系统设计与研制，该仪器可发射不同频率的射频能量同时带有冷却，由阵列式电极，球囊，冷却介质和射频发生器组成，通过电极开闭/电压控制能量，可实现动脉粥样硬化斑块进行适形加热，本项的研究为动脉粥样硬化的治疗提供了新的思路和重要的理论基础。项目发表论文4篇，并多次参加国际学术交流，申请专利11项，培养研究生4人。