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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*

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【作者】 刘勇黄志军袁洪吴小兵彭建强阳国平

【Author】 LIU Yong1, HUANG Zhi-jun2, YUAN Hong2, WU Xiao-bin3, PENG Jian-qiang2, YANG Guo-ping2(1. Institute of Biomedical Engineering, Central South University, Changsha, Hunan 410008, P.R.China; 2.The Center of Experimental Medical Research in the Third Xiangya Hospital, Centre South University, Changsha, 410013, P.R.China; 3.Research and Development Workstation of Virogene Carrier, Biological Field of "863"Program, Beijing 100052, P.R.China)

【机构】 中南大学生物医学工程研究院中南大学湘雅三医院医学实验中心八六三计划生物领域病毒基因载体研发基地中南大学湘雅三医院医学实验中心 湖南长沙410008湖南长沙410013北京100052

【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.

【基金】 湖南省卫生厅科研基金资助项目(No:B2004-065)
  • 【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
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