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人源碱性成纤维细胞因子基因对缺血心肌血管新生的影响
Human basic fibroblast growth factor gene transfer induces angiogenesis in ischemic heart*
【摘要】 目的探讨人源碱性成纤维细胞因子(hbFGF)基因对兔缺血心肌血管生成的影响。方法分别向40只新西兰兔心肌缺血模型的心肌注射1010、1012、1013v.g./Kg的携带hbFGFcDNA的腺相关病毒载体或磷酸盐缓冲液。4周后取心肌组织,采用RT-PCR检测hbFGF基因的表达;并于高倍镜下计数缺血区域新生血管数目。结果随着治疗剂量的增加,治疗各组的hbFGFmRNA表达依次增高,差异均具有显著性(P<0.05)。单个高倍视野(HPF)内的新生血管数分别为(4.52±1.37)、(10.78±1.62)和(18.64±3.32)条,而对照组为(4.46±1.42)条。高、中剂量组的新生血管计数结果显著高于对照组(P<0.05)。结论rAAV-2载体介导的hbFGF基因能诱导缺血心肌血管生成,且呈剂量依赖性。
【Abstract】 s: [Objective] To investigate the effect on ischemic myocardium of human basic fibroblast growth factor (hbFGF) cDNA mediated by recombinant adeno-associated viral vector2 (rAAV-2). [Methods] Rabbit myocardial ischemic models were generated by ligation of the anterior descending coronary artery. All these forty models were randomly divided into 4 groups: FGF high dose group (1012 v.g./kg), FGF middle dose group (1011 v.g./kg), FGF low dose group (1010 v.g/kg) and control group. RAAV-2/hbFGF or PBS was injected into the ischemic myocardium respectively. After 4 weeks, the expression of objective gene was evaluated by RT-PCR. Myocardial capillary counts were calculated to evaluate the proangiogenic effects. [Results] The expression levels of hbFGF mRNA were increased with the increasing dosage of injected rAAV-2/hbFGF. The changes of expression were dose-dependent and there were significant differences among the groups(P <0.05). In rAAV-2/hbFGF 1010, 1011 and 1012 v.g./kg treatment groups, the microvessel counts were(4.52±1.37)/HPF, (10.78±1.62)/HPF and (18.64±3.32)/HPF respectively, while (4.46±1.42)/HPF in control group. There was significant differences between the 1011, 1012 v.g./kg hbFGF gene-treated groups and control group(both P <0.05), but no such difference between between 1010 v.g./kg hbFGF gene-treated group and control group(P >0.05). [Conclusions] HbFGF gene mediated by rAAV-2 can be efficiently transferred into rabbit ischemic heart and induce angiogenesis of myocardium successfully. The proangiogenic effect of hbFGF gene mediated by rAAV-2 is in a dose-independent manner.
【Key words】 basic fibroblast growth factor; recombinant adeno-associated virus; myocardial ischemia; angiogenesis; gene therapy;
- 【文献出处】 中国医学工程 ,China Medical Engineering , 编辑部邮箱 ,2006年01期
- 【分类号】R541
- 【被引频次】5
- 【下载频次】81