碱性成纤维细胞生长因子基因对心肌梗死后冠状血管新生及血管结构的影响

Intramyocardial Injects Naked DNA Encoding Basic Fibroblast Growth Factor to Promote Angiogenesis and Induce the Changes of Coronary Artery Structure in Rabbits with Acute Myocardial Infarction

为探讨心肌内注射碱性成纤维细胞生长因子基因对心肌梗死后冠状血管新生和血管结构的影响。以碱裂解法大量制备质粒 ;采用开胸结扎兔冠状动脉左前室间支法 ,建立兔急性前壁心肌梗死模型。模型制备成功后将动物分为治疗组 (n =1 9)和对照组 (n =1 8) ,并于心肌内分别注射pcDNA3 碱性成纤维细胞生长因子 1 0 0 μg和pcDNA31 0 0 μg,饲养至第 2、6和 1 2周末处死 ;免疫组织化学法观察蛋白表达 ;病理切片观察梗死心肌组织学变化、缺血心肌内血管新生和血管管壁及管腔变化情况。结果发现 :(1 )实验中描记的心电图证实兔急性心肌梗死模型制作成功。 (2 )免疫组织化学观察注射pcDNA3 碱性成纤维细胞生长因子处心肌组织在 6周内有碱性成纤维细胞生长因子蛋白的表达。 (3)病理切片行图象分析计算血管密度发现 :治疗组毛细血管密度和小动脉密度显著高于对照组。 (4 )实验第 6周治疗组与对照组动脉平均管壁厚度分别为 1 9.8± 9.9μm比 1 8.9± 9.6 μm (P >0 .0 5 ) ;1 2周分别为 2 8.3± 1 1 .5 μm比 2 4 .1± 1 1 .3μm (P <0 .0 1 ) ;6周比值分别为 0 .31± 0 .1 6比 0 .2 4± 0 .1 2 (P <0 .0 1 ) ;1 2周分别为 0 .34± 0 .1 5比 0 .2 5± 0 .0 9(P <0 .0 1 )。实验结果提示 ,心肌内注射碱性成纤维细胞生长?

Aim To study the effects of naked DNA encoding basic fibroblast growth factor (bFGF) for treatment acute myocardial infarction in rabbits model. Methods 42 rabbits underwent left thoracotomy followed by the ligation of left anterior descending coronary artery. After model reproducing, the rabbits were randomized to receive a directly intramyocardial injection of either pcDNA3 bFGF (n=19) or pcDNA3 (n=18). 2, 6 or 12 weeks later, immunhistologic analysis was performed to study expression of bFGF gene at protein level. Histologic analysis was performed to evaluate angiogenesis induced by gene therapy. Observing the changes of artery wall by pathology image analysis. Results Changes of electrocardiogram testify that the model of AMI is successful. immunuhistologic analysis shows that bFGF gene can express in ischemic myocardial in 6 weeks. Histologic analysis shows:there was a significant increase in the density of capillaries and anterioles in gene therapy group. Calculated the average wall thickness of the big vessels (diameter≥200 μm ) and the ratios of average wall thickness and vessel diameter by image analysis. In bFGF and control groups the average wall thickness 6W were:19.8±9.9 μm vs 18.9±9.6 μm, P>0.05; 12W: 28.3±11.5 μm vs 24.1±11.3 μm, P<0.01, respectively; ratios of 6W: 0.31±0.16, 0.24±0.12, P<0.01; 12W: 0.34±0.15,0.25±0.09,P<0.01. Conclusion Directly intramyocardial injection of bFGF gene can promote angiogenesis and induce vascular remodeling in ischemic myocardium. Suggesting that bFGF gene may have the possibility to become a new treatment strategy for coronary heart disease.