血管内皮生长因子基因治疗小型猪冠状动脉闭塞的实验研究Direct gene transfer of nacked DNA encoding vascular endothelial growth factor into ischemic swine myocardium
蒋捷,高炜,王日胜,洪涛,肖锋,王进,牛大地,朱国英,周爱儒
摘要(Abstract)：
目的 探讨应用血管内皮生长因子 (VEGF)基因治疗动物实验性冠状动脉闭塞的疗效。方法 中国实验用小型猪 19只 ,结扎左冠状动脉前降支中远段 ,心肌内多点注射自行构建的pcD2 hVEGF1 2 1 真核表达质粒。应用逆转录聚合酶链反应、VEGF免疫组化染色、Ⅷ因子相关抗原免疫组化染色等方法检测VEGF基因在心肌中的表达及其生物学作用 ,用常规冠状动脉造影观察VEGF基因治疗对闭塞冠脉侧支循环建立的作用。结果 转移VEGF基因后 ,小型猪心肌内VEGFmRNA高表达 ,VEGF免疫组化染色提示VEGF蛋白表达水平升高 ;Ⅷ因子相关抗原免疫组化染色显示心肌毛细血管增加 ;冠状动脉造影证明VEGF基因治疗能够促进闭塞冠脉侧支循环的建立。结论 心肌内注射pcD2 hVEGF1 2 1 真核表达质粒能够获得VEGFmRNA和蛋白的有效表达 ,促进心肌毛细血管增生 ,促进侧支循环建立
关键词(KeyWords)： 内皮生长因子;心肌缺血治疗;基因疗法;内皮,血管
基金项目(Foundation): 国家 8 6 3计划生物技术资助项目 ( 86 3 10 2 BHIO3);; 北京市自然科学基金资助项目 ( 7992 0 38)
作者(Author): 蒋捷,高炜,王日胜,洪涛,肖锋,王进,牛大地,朱国英,周爱儒
参考文献(References)：
- 1DvorakHF ,BrownLF ,DetmarM ,etal.Vascularpermeabilityfactor vascularendothelialgrowthfactor,microvascularhyperpermeabilityandangiogenesis.AmJPathology,1995,146:10291034.
- 2BanaiS ,JaklitschM ,ShouM ,etal.Angiogenic inducedenhancementofcollateralbloodflowtoischemicmyocardiumbyvascularendothelialgrowthfactorindogs.Circulation,1994,89:21832189.
- 3Lopez,J ,LahamR ,StamlerA ,etal.VEGFadministrationinchronicmyocardialischemiainpigs.CardiovascRes,1998,40:272281.
- 4RentropKP ,CohenM ,BlankeH ,etal.Changesincoronarycollateralfillingimmediatelyaftercontrolledcoronaryarteryocclusionbyanangioplastyballooninhumansubjects.JAmCollCardiol,1985,5:587592.
- 5BainiS ,ShweikiD ,PinsonA ,etal.Upregulationofvascularendothelialgrowthfactorexpressioninducedbymyocardialischemia:implicationsforcoronaryangiogenesis.CardiovascRes,1994,28:11761179.
- 6LiJ,BrownLF ,HibberdMG ,etal.VEGF ,flk1,andflt1expressioninaratmyocardialinfartionmodelofangiogenesis.AmJPhysiol,1996,270:H1803H1811.
- 7KranzA ,RauC ,KochsM ,etal.ElevationofvascularendothelialgrowthfactorAserumlevelsfollowingacutemyocardialinfarction.Evidenceforitsoriginandfunctionalsignificance.JMolCellCardiol,2000,32:6572.
- 8HouckKA ,LeungDW ,RowlandAM ,etal.Dualregulationofvascularendothelialgrowthfactorbioavailabilitybygeneticandproteolyticmechanisms.JBiolChem,1992,267:2603126037.
- 9盛琴慧,朱国英,周爱儒,等.血管内皮生长因子基因治疗肢体动脉梗塞病的实验研究.中华医学杂志,1999,79:129132.
- 10刘艳秋,周爱儒,朱小君,等.大鼠心肌缺血的血管内皮生长因子基因治疗.北京医科大学学报,1999,31:489492.
- 11SymesJ ,LosordoD ,ValeP ,etal.Genetherapywithvascularendothelialgrowthfactorforinoperablecoronaryarterydisease.AnnThoracSurg,1999,68:830837.