促血管生长因子基因转染促心肌缺血区侧枝循环环成研究

Ischemic heart disease is one of the leading causes of human death. Different from the various therapies of the disease currently in use today, gene therapy is based on the concept of "therapeutic angiogenesis" and makes a very promising therapeutic strategy. The objects of our studies were to compare the biologic potentials of a variety of angiogenic factors, to evaluate their efficacy in the treatment of ischemic heart disease and to provide some guidance for their possible clinical application in future. In our studies, we first established reliable animal models of myocardial ischemia by occluding of coronary arterial branches with ligature or ameroid constrictor. Then we constructed a stable adenovirus vector system, as evidenced by our success in expressing Lac Z gene in porcine ischemic myocardium with the system. Following that, we injected an angiogenic factor, angiogenin derivative Asp116His (ANG-D116H), in its protein form to ischemic myocardium and observed remarkable new blood vessel formation subsequently, showing the feasibility of therapeutic angiogenesis. Thereafter, we transfected ischemic myocardium with aFGF and VEGF-B genes by means of adenovirus-mediated gene transfer and evaluated the results by pathology and echocardiography. As it turned out, neo-angiogenesis was remarkable and performance of the transfected ischemic myocardium was improved to some extent. Our studies demonstrated that gene therapy was effective and safe in treatment of ischemic heart disease, adenovirus vector system was a reliable means for target gene transfection and angiogenic factors such as ANG-D116H, aFGF and VEGF-B were promising factors worthy of further investigation for their future clinical application.

冠心病是导致人类死亡的主要疾病，目前其治疗效果尚不理想。基因治疗能促进心肌缺血区侧枝循环的形成，弥补现有治疗方法的不足。本项目拟用数种代表性的促血管生长活性因子的基因，构成重组腺病毒，单独或联合转染缺血的心肌，以期达到良好的促侧枝循环效果。如获成功，将为今后的临床应用打下坚实的基础，并产生巨大的社会效益和经济效益。