“健康样”血管新生的超声干预与光声评估方法研究

Ischemic disease is the leading killer of human being. Therapeutic angiogenesis is one of the most hopeful treatment therapies. There are two key problem to solve: how to promote the establishment of “healthy” collateral circulation,and how to judge the “healthy” angiogenesis. In our previously study, we have found that low intensity therapeutic ultrasound (TUS) can promote neovascularization ischemic diseases. This time, we’ll focus on these points: (1) Use several different modes (different energy flux density between 0.5-3 MHz, frequency and application time) TUS treatment in mice hindlimb ischemia, and use a high sensitive infrared temperature measurement system to detect “healthy” angiogenesis and then find out the most effective TUS mode. This will solve the first problem. (2) To figure out the character of “healthy” angiogenesis, To establish an alive photoacoustic imaging system to classified the permeability of blood vessels via observing the vessel wall element, blood oxygen content and the morphology of vascular network. (3) To verify the efficacy of TUS and photoacoustic imaging system in vitro an in vivo via biological method. And then investigate the further mechanism of enhanced endothelia cell and the pathway of stimulation of “healthy” angiogenesis events. This program will promote the clinical application of TUS in ischemic vascular diseases and provide the solid evidence.

缺血性疾病是人类健康的头号杀手，促血管新生疗法是最有希望的治疗方法之一。其关键的两个难点是：如何增多具有侧枝循环功能的“健康样”血管比例，及鉴别“健康样”新生血管的方法。我们前期研究已发现，低强度超声干预可有效改善缺血。基于此基础，本课题将重点研究：（1）建立大样本大鼠下肢缺血模型，进行多参数组合的超声模式干预，应用高灵敏的红外测温系统，通过温度间接对“健康样” 新生血管进行快速评估，筛选出超声干预的最佳模式，解决促“健康样”血管新生这一大难题；（2）建立体内新生血管光声成像方法，开展对血管壁成分、血氧含量和血管网络的形态成像，对血管渗透性进行分级评估，破解评判血管通透性的光声检测难题；（3）应用生物学方法，验证超声干预和光声评估方法的有效性，并基于此探索超声干预增强内皮细胞活性和促进内源性血管生成因子的途径，为促血管新生疗法应用于临床提供可靠的理论和实验基础。

缺血性疾病是人类健康的头号杀手，促血管新生疗法是最有希望的治疗方法之一。其关键的两个难点是：如何增多具有侧枝循环功能的“健康样”血管比例，及鉴别“健康样”新生血管的方法。我们前期研究已发现，低强度超声干预可有效改善缺血。基于此基础，本课题重点研究了：（1）建立大样本大鼠下肢缺血模型，进行多参数组合的超声模式干预，应用高灵敏的红外测温系统，通过温度间接对“健康样” 新生血管进行快速评估，筛选出超声干预的最佳模式，解决促“健康样”血管新生这一大难题；（2）建立体内新生血管光声成像方法，开展对血管壁成分、血氧含量和血管网络的形态成像，对血管渗透性进行分级评估，破解评判血管通透性的光声检测难题；（3）应用生物学方法，验证超声干预和光声评估方法的有效性，并基于此探索超声干预增强内皮细胞活性和促进内源性血管生成因子的途径，为促血管新生疗法应用于临床提供可靠的理论和实验基础。