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冠状静脉窦逆行灌注血管内皮生长因子基因对心肌梗死兔模型基质金属蛋白酶表达的影响
Coronary sinus retrograde perfusion pAdtrackCMV-VEGF165 modulates MMPs expression in rabbit myocardial infarction model
【摘要】 目的观察经冠状静脉窦逆行灌注血管内皮生长因子基因(pAdtrackCMV-VEGF165)对兔心肌梗死模型左心室心肌组织基质金属蛋白酶(MMP 1,2)及其组织抑制因子(TIMP1,2)表达的影响。方法20只新西兰大白兔随机分为基因治疗组和对照组,两组动物常规全麻,气管插管,胸骨正中切开,暴露心脏,结扎左室支建立心肌梗死模型,冠状静脉窦插管,基因治疗组逆行灌注pAdtrackCMV-VEGF165,对照组以生理盐水对照,全程记录心电,于结扎左室支前及结扎后6h取冠状静脉窦血4mL备测CK、CK-MB及TnT。4周后处死动物,取左心室前壁心肌检测MMP 1,2、TIMP 1,2表达情况,并计算TIMP1/MMP1比值。结果对照组1只动物于术后1d死亡,基因治疗组所有动物全部存活;结扎后即刻可见左室前壁及心尖部颜色变暗,搏动减弱,心电图出现ST段抬高并与T波融合;结扎后6h CK、CK-MB及TnT均显著高于结扎前(P<0.05或0.01);基因治疗组MMPI表达增强(P<0.05),TIMP 1、MMP 2及TIMP 2表达与对照组差异无显著,TIMP 1/MMP 1明显低于对照组(P<0.01)。结论经冠状静脉窦逆行灌注pAdtrackCMV-VEGF165可调节基质金属蛋白酶及其组织因子表达,改善梗死后心室重塑。
【Abstract】 Objective To investigate the effect of VEGF gene transfer on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPS) expression by coronary sinus retrograde perfusion with pAdtrackCMV-VEGF165 in rabbit myocardial infarction model.Methods Twenty New Zealand rabbits were divided into 2 groups,general anesthesia and open thorax,elevating the apex of the heart,clamping the main stem of left ventricular coronary,pAdtrackCMV-VEGF165 were retrograde perfused trough coronary sinus in experiment group,and nature saline were used in control group.Expression of MMP1,2 and TIMP1,2 were detected 4 weeks later.The ratio of TIMP1/ MMP1 was calculated.Results One animal died of heart failure in control group and all animal survived in gene treatment group.The expression of MMP1 were lower in control group (P<0.05).The ratio of TIMP1/MMP1 were significantly higher in control group than that in gene treatment group (P< 0.05).Conclusion Coronary sinus retrograde perfusing with pAdtrackCMV-VEGF165 can modulate the expression of MMPs and TIMPs,thus,improve ventrencle remodeling.
【Key words】 Coronary sinus retrograde perfusion; VEGF; Gene; Rabbit; Myocardial infarction;
- 【文献出处】 贵州医药 ,Guizhou Medical Journal , 编辑部邮箱 ,2010年06期
- 【分类号】R654.2
- 【下载频次】20