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血管内皮生长因子基因治疗犬闭塞性血管病的初步研究 |
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Preliminary study on treatment of limb ischemia with VEGF gene
郑卫 霍勇 邢德智 陈光慧 高炜 朱国英 汤健 周爱儒
Zheng Wei, Huo Yong, Xing Dezhi, et al
【摘要】 目的 探讨血管内皮生长因子(VEGF)基因治疗犬闭塞性血管病的可行性，
并对其安全性进行初步观察。方法 构建了重组VEGF基因的真核表达载体。在基因转
移前3天，肌肉内注射肌肉再生剂丁哌卡因(bupivacaine)，并通过基因缝线和直接注射
法，向血管闭塞症犬(n=5)的肌肉内转移重组VEGF基因(0.5 mg/kg)，应用RT-PCR技术
观察VEGF基因的表达，通过血管造影观察VEGF基因导入犬体内的生物效应；并应用临
床自动血液生化分析仪和眼底镜进行转基因的安全性观察。结果 转pcDNA3/VEGF基
因28天后，缺血区肌肉组织内VEGF的表达明显高于对照单纯转pcDNA3组；14天后血管
造影可见明显新生血管和侧枝循环的形成，28天后更明显，一年后未见血管无限制生
长；血液生化测定未见明显副作用。结论 肌肉内转移VEGF基因通过促进血管新生和
侧枝循环建立，促进血流恢复，经一年连续观察，无明显毒副作用，为闭塞性血管病
的治疗，提供一种新的有效方法。
【关键词】 内皮生长因子 基因疗法 侧支循环
Preliminary study on treatment of limb ischemia with VEGF gene Zheng Wei, Huo Yong,
Xing Dezhi, et al. Institute of Cardiovascular Research, Beijing Medical University, Beijing 100083
【Abstract】 Objective To sutdy the feasibility and security of using VEGF gene directly for
treating limb ischemia.Methods The human VEGF cDNA was cloned into eukaryotic expression
vector pcDNA3. Three days after bupivacaine treatment for muscle regeneration, the recombinant
plasmids were transferred by gene suture and injection into the adductor of dogs (n=5), of which
the distal extreme of external iliac artery was ligated. The expression, biological effect and security
of VEGF gene in the experimental animal were investigated with RT-PCR, angiography and automatic
blood biochemistry analyzer.Results The expression of VEGF gene in the experimental group was
significantly higher than those of control group. Twenty eight days after the initiation of therapy,
angiography showed that the transfer of VEGF gene stimulated the formation of focal neovessels
and established collateral circulation, but did not induce unlimited vascularization one year later.
Conclusion The results demonstrate that VEGF gene therapy to treat[1] [2] 下一页
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