肌肉电转促血管形成素-1基因治疗大鼠下肢血管闭塞病

摘要

Objective　We tested the hypothesis that gene transfer of plasmid DNA encoding angiopoietin-1 (Ang-1) could modulate collateral vessel development in a rat model of hindlimb ischemia. Methods　PcD2 and pcD2 / Ang-1 were electroporated intramuscularly into the rat ischemic hindlimb. Couateral vessel development and limb perfusion were assessed by capillary density, capillary / muscle fiber ratio, angiograghy and clinical observation. Results　(1) The expression of Ang-1 gene was comfirmed RT-PCR and immunohistochemistry; (2) Collateral vessels developed more with pcD2/Ang-1 than those with pcD2. Conclusion　Intramuscular electroporation of Ang-1 gene produces anatomic and physiological evidence of enhanced collateral vessels formation. Ang-1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia.%目的观察肌肉电转促血管形成素-1（angiopoietin-1，Ang-1）基因对大鼠下肢血管闭塞病的治疗效果。方法制作大鼠下肢血管闭塞病模型，通过电转Ang-1进行基因治疗，以RT-PCR及免疫组化方法观察Ang-1基因的表达，应用微血管计数、血管造影技术及相关临床指标观察Ang-1基因导入大鼠体内的生物学效应。结果（1）肌肉电转pcD2Ang-1基因可在大鼠局部转基因肌肉组织高效表达Ang-1；（2）转pcD2Ang-1基因组大鼠下肢肌肉组织新生血管及侧支循环数目明显多于同期空载质粒对照组。结论转Ang-1基因可促进大鼠局部组织新生血管形成和侧支循环建立，恢复闭塞部位血供，从而有效治疗血管闭塞病。