血管生成素1基因上调Tie2受体表达促进大鼠急性心肌梗死血管生成的实验研究Upregulation of Tie2 receptor and enhancement of angiogenesis and arteriogenesis by gene transfer of angiopoietin-1 in rat models of acute myocardial infarction
孙丽杰,崔鸣,冯新恒,王佐岩,马康涛,毛节明,沈丽,陈凤荣,周春燕
摘要(Abstract)：
目的 通过观察血管生成素 1 (angiopoietin 1 ,Ang1 )基因对急性心肌梗死大鼠心肌Tie2受体表达的影响 ,探讨Ang1基因治疗促进血管生成 ,减少梗死面积的可能机制。方法 结扎左前降支冠状动脉制备大鼠心肌梗死模型 ,心肌内分别直接注射空载质粒或phAng1质粒 ;分别于术后第 3,7,1 4 ,2 8天取材 ,利用RT PCR技术分析心肌组织内Tie2受体表达 ;免疫组化方法计算血管生成以及肌性小动脉生成数量 ,Masson染色法检测心肌梗死面积。结果 Ang1基因治疗组Tie2受体mRNA表达明显高于对照组 ,于术后 7天达到高峰 ,2 8天降至正常水平。术后第 7,1 4和 2 8天 ,Ang1基因治疗组的血管生成及肌性小动脉生成较同期对照组均明显增加 ,梗死面积减小。结论 Ang1基因心肌内注射促进急性心肌梗死血管生成及肌性小动脉生成 ,减小梗死面积 ,其机制可能与促进Tie2受体上调有关。
关键词(KeyWords)： 心肌梗死;血管生成因子;基因疗法
基金项目(Foundation): 北京大学医学部“十五”2 11工程 (10 4 4 ) ;; 教育部博士点基金 (2 0 0 10 0 0 10 96) ;; 国家自然科学基金 (3 0 3 715 62 )
作者(Author): 孙丽杰,崔鸣,冯新恒,王佐岩,马康涛,毛节明,沈丽,陈凤荣,周春燕
参考文献(References)：
- 1ThurstonG ,SuriC ,SmithK ,etal.Leakage resistantbloodvesselsinmicetansgenicallyoverexpressingangiopoietin1.Science,1999,286:25112514.
- 2MatsunoH ,KozanaO ,YoshimiN ,etal.Lackofalpha2 antiplasminpromotespulmonaryheartfailureviaoverreleaseofVEGFafteracutemyocardialinfarction.Blood,2002,100:24872493.
- 3WitzenbichlerB ,MaisonpierrePC ,JonesP ,etal.Chemotacticpropertiesofangiopoietin1and2,ligandsfortheendothelial specificreceptortyrosinekinaseTie2.JBiolChem,1998,273:1851418521.
- 4PapapetropoulosA ,GarciaCardenaG ,DenglerTJ ,etal.Directactionsofangiopoietin1onhumanendothelium:evidencefornetworkstabilization,cellsurvival,andinteractionwithotherangiogenicgrowthfactors.LabInvest,1999,79:213223.
- 5ShyuKG ,ManorO ,MagnerM ,etal.DirectintramuscularinjectionofplasmidDNAencodingangiopoietin1butnotangiopoietin2augmentsrevascularizationintherabbitischemichindlimb.Circulation,1998,98:20812087.
- 6祖凌云,蒋捷,姜宁,等.联合促血管生成素1及血管内皮生长因子基因治疗对大鼠新生血管通透性的影响.中国介入心脏病学杂志,2004,12:107109.
- 7WilliamC ,KoehneP ,J櫣rgensenJS,etal.Tie2ReceptorExpressionIsStimulatedbyHypoxiaandProinflammatoryCytokinesinHumanEndothelialCells.CirculationResearch,2000,87:370377.
- 8ShyuKG ,LiangYJ ,ChangH ,etal.Enhancedexpressionofangiopoietin2andtheTie2receptorbutnotangiopoietin1ortheTie1receptorinaratmodelofmyocardialinfarction.JBiomedSci,2004,11:163171.
- 9Nyk nenAI ,KrebsR ,SaaristoA ,etal.Angiopoietin1ProtectsAgainsttheDevelopmentofCardiacAllograftArteriosclerosis.Circulation,2003,107:13081314.
- 10SatoTN ,TozawaY ,DeutschU ,etal.DistinctrolesofthereceptortyrosinekinasesTie1andTie2inbloodvesselformation.Nature,1995,376:7074.