超声分子成像在体评价突变型低氧诱导因子-1alpha基因在老年鼠缺血下肢血管新生的实验研究

治疗性血管新生是当前心血管领域的前沿热点，它的出现有望为缺血性心血管疾病的治疗提供新的途径。现有的动物实验研究虽取得令人兴奋的成绩，但大型的临床试验结果却不尽人意。其中，缺乏早期、无创、有效的评价手段及合适的动物模型可能是动物实验和临床试验结果相悖的重要原因。因此，如果能在更符合临床情况的动物模型中早期、无创、有效的评价治疗性血管新生无疑具有重要的临床意义。本项目拟在本实验室前期相关研究的基础上构建老年鼠下肢缺血模型，并分别转染重组腺病毒包裹的不同突变位点的低氧诱导因子-1a基因，以新生血管内皮细胞特异性靶分子av-整合素为靶标制备靶向超声微泡，应用超声分子成像技术评价突变型低氧诱导因子-1a在老年鼠缺血下肢的血管新生效应并进一步探讨突变型低氧诱导因子-1a促血管新生的机制。

Therapeutic angiogenesis is the current focus in the field of cardiovascular research and represents a potential therapeutic approach for the treatment of patients with advanced coronary or peripheral artery disease. Numerous animal studies have established that angiogenesis of ischemic tissue can be enhanced with exogenous growth factors or vascular progenitor cells, and clinical studies have been initiated. However, clinical trials to date are negative or give conflicting results. The inability to noninvasively assess the angiogenic response and the inappropriate model tested may be the potential explanations for the failure of previous clinical trials. Therefore, it will be of great clinical significance if we can erly assess angiogenesis effectively in an animal model more consistent with the clinical situation. In this study, we constructed HIF-1a mutants with two or three point mutations (HIF-1a402/564 and HIF-1a402/564/803, respectively)to evaluate their angiogenic effect in an aged mice hind-limb ischemia model by ultrasound molecular imaging with microbubbles bearing av-integrins antibody and further investigate the mechanisms for the enhanced neovascularization by HIF-1a mutants.