腺病毒介导的血管内皮生长因子165对兔外周血管生成作用的研究

The effect of adenovirus-mediated vascular endothelial growth factor 165 on angiogenesis in acute ischemic hindlimb of rabbit

目的 :检验以腺病毒为载体的血管内皮生长因子 16 5 (Ad VEGF16 5 )基因的表达规律及能否促进缺血骨骼肌血管生成。方法 :将兔右股动脉离断后 ,在缺血肌肉组织中直接注入Ad VEGF16 5或磷酸盐缓冲液 (PBS) ,5周后 ,以血管造影、免疫组化检查及单光子发射计算机断层 (SPECT)显像检测局部缺血组织血管新生情况。用酶联免疫分析法 (ELISA)检测血浆和肌肉组织中Ad VEGF16 5的表达。结果 :Ad VEGF16 5注入缺血肌肉组织后 2 4h达到表达高峰 ,1周时降至基线水平 ,血浆及对侧健康的肌肉组织中无目的基因表达 ,治疗组缺血肢体侧枝血管 (P <0 0 1)、血管密度 (P <0 0 5 )及相对血流 (P <0 0 1)均明显高于对照组。结论 :缺血肌肉组织中直接注入Ad VEGF16 5可诱导局部VEGF蛋白表达 ,促进缺血部位的血管生成 。

Objective:To investigate the efficacy on inducing angiogenesis and the expressing of the adenovirus mediated vascular endothelial growth factor 165 (Ad VEGF165) in ischemic muscles.Methods:New Zealand White rabbits underwent ligation of femoral artery and injection of Ad VEGF165 or phosphate buffered saline (PBS) solution into the ischemic thigh muscles The angiography ,single photon emission computer tomography (SPECT) imaging and immunohistochemistry assay were carried out to evaluate the angiogenesis in the ischemic region 5 weeks later and enzyme linked immunoassay (ELISA) was done to investigate the local expression of Ad VEGF165 in the injected muscles.Results:The peak expression of Ad VEGF165 occured 24 hours after the administration of Ad VEGF165 and decreased gradually to control level by seven days The collateral vessels ( P <0 01) ,vascular density ( P <0 05) and relative blood flow ( P <0 01) increased significantly in the therapy group compared with control group. Conclusion:Local intramuscular injection of Ad VEGF165 results in transient local expression of the VEGF,induces angiogenesis and enhances blood flow in the ischemic muscles of the New Zealand White rabbits.