血管内皮生长因子基因治疗犬闭塞性血管病的初步研究  

Preliminary study on treatment of limb ischemia with VEGF gene

作　　者：郑卫[1] 霍勇[1] 邢德智[1] 陈光慧[1] 高炜[1] 朱国英[1] 汤健[1] 周爱儒[1] 

机构地区：[1]北京医科大学心血管研究所

出　　处：《中华心血管病杂志》1998年第1期62-64,共3页Chinese Journal of Cardiology

基　　金：国家八六三项目

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（０．５ｍｇ／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。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 pcDNA 3. 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 tissue ischemia might be feasible and safe and represent a potential therapeutic strategy.

关 键 词：血管疾病 闭塞性 内皮生长因子 基因治疗 

分 类 号：R543.05[医药卫生—心血管疾病]