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目的确定穿心室壁内支架联合血管内皮生长因子基因治疗在猪急性心肌梗死(AMI)模型中的治疗作用。方法中国小型猪30头随机分为四组:心肌梗死组(MI);支架组(ST);内皮生长因子基因组(VEGF)和支架+基因组(ST+VEGF)。MI组采用结扎冠状动脉左前降支形成AMI模型,其余三组在形成梗死模型后分别采用穿心室壁支架置入、直接心肌内注射携带hVEGF165的质粒载体以及联合治疗。4周后行心脏超声、心肌血管密度检测和免疫组化等检查。结果4周后ST组、VEGF组、ST+VEGF组的血管密度均明显多于MI组,其中ST+VEGF组与其他各组比较在促进血管生长方面有明显优势(P<0.01)。VEGF组和ST+VEGF组较MI组在VEGF蛋白表达方面明显提高。结论穿心室壁内支架联合VEGF治疗综合了支架形成通道、机械刺激促进血管生成以及携带促血管生成因子基因的载体的输送作用,提供了一种比任何单独治疗心肌梗死技术更有效的手段。
Objective To determine the therapeutic effect of intravascular wall stent combined with vascular endothelial growth factor gene therapy in swine acute myocardial infarction (AMI) model. Methods Thirty Chinese miniature pigs were randomly divided into four groups: MI group, ST group, VEGF and ST + VEGF group. The AMI model was established by ligation of the left anterior descending coronary artery in MI group, and the other three groups were treated by percutaneous transluminal coronary angioplasty with direct injection of plasmid vector and combination therapy of hVEGF165. After 4 weeks, cardiac ultrasound, myocardial vascular density test and immunohistochemistry were performed. Results After 4 weeks, the vascular densities of ST group, VEGF group and ST + VEGF group were significantly higher than those of MI group. The ST + VEGF group showed obvious advantages in promoting blood vessel growth compared with other groups (P <0.01). Compared with MI group, the expression of VEGF protein in VEGF group and ST + VEGF group increased obviously. CONCLUSIONS The combination of intra-aortic transluminal stent placement and VEGF therapy incorporates scaffold-forming channels, mechanical stimulation of angiogenesis, and delivery of vectors carrying pro-angiogenic factors, providing a more effective means of treatment than any single agent for myocardial infarction.