血管内皮生长因子基因多态性与急性心肌梗死的相关性研究

分类号：五号宋体字密级：五号宋体字UDC：五号宋体字学校代码：11065指导教师姓名及专业技术职务四号宋体学科专业名称四号宋体字论文提交日期实际提交日期填写四号宋体字论文答辩日期评阅时可填待定时间或为空答辩委员会主席评阅时此项若待定可为空（此封面模版只限答辩前论文评阅使用，通过答辩后修改定稿的学位论文，请使用校学位办公室统一印制的封面装订）血管内皮生长因子基因多态性与急性心肌梗死的相关性研究摘要目的：急性心肌梗死(acutemyocardialinfarction，AMI)冠状动脉急性、持续性缺血缺氧所引起的心肌坏死。临床上多有剧烈而持久的胸骨后疼痛，休息及硝酸酯类药物不能完全缓解，伴有血清心肌酶活性增高及进行性心电图变化，可并发心律失常、休克或心力衰竭，常可危及生命。血管内皮生长因子(vascularendothelialgrowthfaetor，VEGF)是对血管内皮细胞有高度特异性的有丝分裂原，高浓度的VEGF可有效促进血管内皮细胞生长、分化及迁移，诱导新生血管形成，促进体内组织建立起丰富毛细血管网；并且可增加毛细血管后静脉和小静脉通透性，而且还与心肌梗死患者免疫功能低相关。VEGF基因具有高度多态性，目前至少发现了30多个单核昔酸多态性(SNP)位点。本研究通过检测入选的急性心肌梗死患者的VEG血清浓度、VEGF的SNPs、生化、血常规、尿常规等，进行如下分析：1．VEGF基因SNPs与AMI发病风险的关联分析；2.血浆VEGF浓度与VEGF基因SNPs的关系；3.VEGF血浆水平与MACCE发生率相关性；4．LV-remodling与VEGF浓度及多态性的相关性；5.心肌梗死面积分别与VEGF血清浓度及VEGF的SNP的相关性。为急性心肌梗死的研究提供更多的临床数据参考。方法：采用基于医院的病例一对照研究方法，将入选的患者分为急性心肌梗死患者组（研究组）和对照组，检测入选的急性心肌梗死患者的VEGF血清浓度、VEGF的SNPs、生化、血常规、尿常规；检测随访6月后的左室功能（左室重塑）；AMI发生6个月后再行如下检查：a．研究对象随访观测MACCE；b.行核素心肌显像测定心肌面积；c.行超声心动图测定左室重构。通过记录6个月内的心血管事件发生率。对比和研究以下数据：1．VEGF基因SNPs与AMI发病风险的关联分析；2.血浆VEGF浓度与VEGF基因SNPs的关系；3.VEGF血浆水平与MACCE发生率相关性；4．LV-remodling与VEGF浓度及多态性的相关性；5.心肌梗死面积分别与VEGF血清浓度及VEGF的SNP的相关性。结果：通过对比和研究以下数据：1．VEGF基因SNPs与AMI发病风险的关联分析，结果表明VEGF基因SNPs与急性心肌梗死正相关（r=0.312）；2.血浆VEGF浓度与VEGF基因SNPs的关系成正相关(r=0.573)；3.VEGF血浆水平与MACCE发生率相关性分析表明，VEGF血浆水平、多态性与MACCE正相关（r=0.618）；4．LV-remodling与VEGF浓度及多态性正相关(r=0.187)；5.心肌梗死面积分别与VEGF血清浓度及VEGF的SNP的相关性结果表明，心肌梗死面积与VEGF血清浓度成正相关（r=0.736），心肌梗死面积与VEGF的SNP成正相关（r=0.582）。结论：血管内皮生长因子的检测数据与急性心肌梗死其他检测的数据相关性分析表明，各数据间均呈正相关，对急性心肌梗死的血管内皮生长因子的检测对急性心肌梗死的研究诊断具有重要意义。关键词：血管内皮生长因子；急性心肌梗死；单核苷酸多态性；血管生成；易感性AbstractObjective：Acutemyocardialinfarction(acutemyocardialinfarction,AMI)coronaryacutemyocardialischemiaandhypoxiacausedbypersistentnecrosis.Aftermorethanaclinicallysevereandpersistentchestpain,restandnitratescannotcompleteremission,accompaniedbyincreasedserumenzymeactivityandsexualECGchanges,maybecomplicatedbyarrhythmias,shockorheartfailure,andoftenlife-threatening.Vascularendothelialgrowthfactor(vascularendothelialgrowthfaetor,VEGF)isavascularendothelialcellshavehighlyspecificmitogen,ahighconcentrationofVEGFcaneffectivelypromotevascularendothelialcellgrowth,differentiationandmigration,induceangiogenesis,andpromotethebodyorganizationsSincetherichcapillarynetwork;andaftertheincreasepermeabilityofcapillariesandvenulesveins,butalsoassociatedwithlowerimmunefunctioninpatientswithmyocardialinfarction.VEGFgeneishighlypolymorphic,currentlyfoundatleastmorethan30single-coreXiacidpolymorphism(SNP)sites.Inthisstudy,serumconcentrationsofselectedVEGdetectionofacutemyocardialinfarction,VEGFofSNPs,biochemistry,blood,urine,etc.,makethefollowinganalysis:1.VEGFgeneSNPsassociatedwithAMIriskanalysis;2betweenplasmaconcentrationofVEGFandVEGFgeneSNPsin;3.VEGFplasmalevelscorrelatedwiththeincidenceofMACCE;4.LV-remodlingpolymorphismandVEGFconcentrationandcorrelation;5infarctsize,respectively,serumconcentrationsofVEGFandVEGFSNPcorrelation.Providemoreclinicaldatareferenceforthestudyofacutemyocardialinfarction.Methods：Acase-controlstudyofhospital-basedapproach,thepatientwillbeenrolledintopatientswithacutemyocardialinfarction(studygroup)andthecontrolgroup,theserumconcentrationsofVEGFselectedpatientswithacutemyocardialinfarction,VEGFofSNPs,biochemistry,blood,urine;detectionfollowedupfor6monthsafterleftventricularfunction(leftventricularremodeling);AMIoccurredsixmonthsaftercheckthefollowing:a.Studyfollow-upobservationsMACCE;.B-linedeterminationofcardiacradionuclidemyocardialperfusionimagingarea;.Cechocardiographyleftventricularremodeling.Byrecordingtheincidenceofcardiovasculareventswithinsixmonths.Compareandstudythefollowingdata:1.VEGFgeneSNPsassociatedwithAMIriskanalysis;2betweenplasmaconcentrationofVEGFandVEGFgeneSNPsin;3.VEGFplasmalevelscorrelatedwiththeincidenceofMACCE;4.LV-remodlingpolymorphismandVEGFconcentrationandcorrelation;5infarctsize,respectively,serumconcentrationsofVEGFandVEGFSNPcorrelation.Results：Bycomparingandresearchthefollowingdata:1.VEGFgeneSNPsassociatedwiththeriskofAMIanalysisshowedthatVEGFgeneSNPsareassociatedwithacutemyocardialinfarction(r=0.312);.2plasmaconcentrationofVEGFandVEGFgeneSNPsinrelationtoapositivecorrelation(r=0.573);3.VEGFplasmalevelsandtheincidenceofMACCEcorrelationanalysisshowedthat,VEGFplasmalevelsofpolymorphismandMACCEpositivecorrelation(r=0.618);4.LV-remodlingpositivecorrelationwithVEGFconcentrationandpolymorphism(r=0.187);.5infarctsizewereserumconcentrationsofVEGFandVEGFSNPcorrelationresultsshowedthatthemyocardialinfarctsizeandserumVEGFconcentrationswerepositivelycorrelated(r=0.736),myocardialinfarctsizeandVEGFSNPpositivecorrelation(r=0.582).Conclusions：Vascularendothelialgrowthfactorcorrelationanalysisofthedataandtestingdatatootherdetectionofacutemyocardialinfarctionshowedapositivecorrelationbetweenthedata,thedetectionofvascularendothelialgrowthfactorinpatientswithacutemyocardialinfarctionhasimportantsignificanceforthestudyofthediagnosisofacutemyocardialinfarction.Keywords:Vascularendothelialgrowthfactor;acutemyocardialinfarction;singlenucleotidepolymorphism;angiogenesis;susceptibility目录引言..................