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1、通心络胶囊对载脂蛋白E基因敲除小鼠冠状动脉粥样硬化的影响及其机理研究论文.freelechanismofTongxinluocapsuleintreatingatherosclerosis(AS)ofcoronaryheartdiseasebymeasuringthechangesofcoronaryplaques,myocardialhistopathologyandcirculatingendothelialcell(CEC),endothelin(ET),matrixmetalloproteina
2、se-1(MMP-1),matrixmetalloproteinase-9(MMP-9),tissueinhibitorsofmatrixmetalloproteinase1(TIMP1)ofApolipoproteinEgeneknockoutmiceApoE(-/-)intervenedbyTongxinluocapsule.MethodsFortyApolipoproteinEgeneknockoutmiceApoE(-/-)entalgrouptoestablishthemodelsofcoro
3、naryatherosclerosis,andrandomlydividedinto5groups(modelgroup,Simvastatingroupandhigh,middle,loentgroupsvastaincapsulescorrespondingly,iceasthenormalcontrolgroup.Thechangesofcoronaryplaques,myocardialhistopathologyandCEC,ET,MMP-1,MMP-9,TIMP1ineachgroupice
4、ofthemodelgroupostlylocatedatsmallbranchesincardiacmuscle,cardiacmuscle,cell,myocardialinterstitium,andtheaveragescorevastatingroupiddle,highdosesofTongxinluocapsuleodelgroup,alltreatmentgroupshadsignificantdifference(P0.05orP0.01).Therevastatingroupandh
5、ighandmiddledoseofTongxinluogroup(P0.05).BloodCECofthemodelgroupincreasedconsiderablyparedalgroup(P0.01)fromthefourthiddledoseofTongxinluocapsule(P0.05)atthefourth,todelgroupalgroup(P0.05)andthreeTongxinluogroups(P0.01).MMP-1andMMP-9ofthemodelgroupiddled
6、osegroupodelgroup.ConclusionTongxinluocapsulecanresistASandstabletheplaques,themechanismisinconnectionodifyingendothetialdysfunction(EDF)andrestrainingvasoconstriction.Keyice;coronaryatherosclerosis;histopathology;CEC;ET;MMP;TIMP1通心络胶囊(以下简称“通心络”)是治疗冠心病(C
7、HD)临床疗效显著的中成药1,但其作用机制仍在探究。本实验通过观察其对载脂蛋白E基因敲除ApoE(-/-)小鼠冠状动脉斑块和心肌病理组织学及其循环内皮细胞(CEC)、内皮素(ET)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂1(TIMP1)等指标的干预并研究其治疗CHD动脉粥样硬化(AS)的疗效机制。现将结果报道如下。1实验材料1.1药物及试剂通心络胶囊,石家庄以岭药业股份有限公司生产,批号20060501;辛伐他汀片,杭州默沙东制药有限公司,批号200
8、653。ET试剂盒由北京东亚免疫技术研究所提供,批号2006058;CEC试剂盒,由南京聚力生物制品工程公司提供,批号200601;MMP-1、MMP-9、TIMP1测定试剂盒,购自晶美生物工程有限公司,美国OrionoDiagostica公司生产,批号00604;胆固醇,上海生化试剂厂,批号051124;甲醛,南京化学试剂厂,批号20040201。1.2动物ApoE(-/-)小鼠40只,8周龄,雌雄各半,体重18~22g,北京大学实验动物