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方立,黄钦,黄芳,李迎,祁珩,张银妆.t-PA基因修饰的内皮祖细胞对大鼠急性心肌梗死的治疗作用[J].中国动脉硬化杂志,2019,(3):204~210
t-PA基因修饰的内皮祖细胞对大鼠急性心肌梗死的治疗作用
Therapeutic effect of t-PA modified endothelial progenitor cells on acute myocardial infarction in rats
投稿时间:2018-08-28  修订日期:2018-12-23
DOI:
中文关键词:  组织型纤溶酶原激活物  内皮祖细胞  急性心肌梗死
英文关键词:tissue plasminogen activator  endothelial progenitor cells  acute myocardial infarction
基金项目:湖南省自然科学基金(2018JJ6127);湖南省卫生计生委科研计划B类课题项目 (B20180471);长沙市科技局项目(K15ZD022-33;Kq1701007)
作者单位E-mail
方立 长沙市第一医院心血管内科二病区,湖南省长沙市 410008 e-mail为527384528@qq.com,e-mail为804962763@qq.com 
黄钦 长沙市第一医院心血管内科二病区,湖南省长沙市 410008  
黄芳 长沙市第一医院心血管内科二病区,湖南省长沙市 410008  
李迎 长沙市第一医院心血管内科二病区,湖南省长沙市 410008  
祁珩 长沙市第一医院心血管内科二病区,湖南省长沙市 410008  
张银妆 长沙市第一医院心血管内科二病区,湖南省长沙市 410008 e-mail为527384528@qq.com,e-mail为804962763@qq.com 
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中文摘要:
      目的 探讨组织型纤溶酶原激活物(t-PA)基因修饰的脐血内皮祖细胞(EPCs)移植治疗对大鼠急性心肌梗死的治疗作用。方法 体外扩增EPCs,将构建的t-PA基因慢病毒表达载体转染脐血EPCs,建立大鼠心肌梗死模型,实验随机分为PBS组、空载体EPCs组、单纯EPCs组和t-PA EPCs组。大鼠急性心肌梗死术后3 h开始移植治疗,t-PA EPCs组、EPCs组和空载体EPCs组静脉注射t-PA基因转染的EPCs、单纯EPCs和空载体EPCs。移植4周后,采用心脏超声评价心脏功能及检测血浆N末端B型脑钠钛前体(NT-Pro-BNP)的表达水平,Western-blot检测心肌组织中血管内皮生长因子(VEGF)、基质金属蛋白酶2/基质金属蛋白酶9(MMP-2/MMP-9)及基质金属蛋白酶组织抑制因子(TIMP-1)的表达水平;移植8 h后,ELISA法检测血清中t-PA、D-二聚体、纤溶酶原激活物抑制物1(PAI-1)和纤维蛋白原(Fib)表达情况。结果 与PBS组、空载体EPCs组以及单纯EPCs组比较,t-PA基因修饰EPCs可明显改善心肌梗死后大鼠的心肌组织病理改变,大鼠急性心肌梗死心功能各参数改善最为显著;t-PA EPCs组NT-Pro-BNP的表达水平显著低于其他各组;t-PA EPCs组VEGF和TIMP的表达水平显著高于其他各组;相反,基质金属蛋白酶(MMP-2/MMP-9)的表达水平显著低于其他各组。t-PA EPCs组t-PA、D-二聚体表达均显著高于其他各组,而PAI-1、Fib表达均显著低于其他各组。结论 t-PA基因修饰的EPCs移植能有效治疗大鼠急性心肌梗死,其具体治疗作用与其改善心脏功能、促进血管新生、抑制心室重构、抑制血栓形成或增加溶栓作用等有关。
英文摘要:
      Aim To investigate the therapeutic effect of tissue plasminogen activator(t-PA) gene modified umbilical cord blood endothelial progenitor cells (EPCs) transplantation on acute myocardial infarction in rats. MethodsEPCs were expanded in vitro,the slow virus expression vector of t-PA gene was transfected into endothelial progenitor cells to establish rat myocardial infarction model,the experiment was randomly divided into 4 groups:PBS solution group, EPCs group transfected with empty vector, simple EPCs group and EPCs group transfected with t-PA gene. Transplantation was started after acute myocardial infarction 3h in rats, t-PA EPCs group, EPCs group, and empty vector EPCs group were injected with T-PA gene-transfected EPCs, EPCs, and empty vector EPCs. Four weeks after transplantation, cardiac function were evaluated by echocardiography and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) expression level was detected,then the expression levels of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-2/matrix metalloproteinase-9 (MMP-2/MMP-9) and Tissue inhibitor of metalloproteinase(TIMP) in myocardial tissue were detected by Western-blot. Eight hours after transplantation, the expression of t-PA, D-Dimer, fibrin degradation products(FDP), plasminogen activator inhibitor 1 (PAI-1) and fibrinogen (Fib) in serum was detected by ELISA. Results Compared with PBS solution group, empty carrier EPCs group and simple EPCs group,the effect of t-PA gene modified EPCs was the most significant in improving various parameters of cardiac function in rats with acute myocardial infarction. The expression level of NT-Pro-BNP in t-PA EPCs group was significantly lower than that in other groups. The expression level of VEGF and TIMP in t-PA EPCs group was significantly higher than that in other groups. On the contrary, the expression level of metalloproteinase (MMP-2/MMP-9) was significantly lower than that of other groups. The expressions of t-PA and D-dimer in t-PA EPCs group were significantly higher than those in other groups, while PAI-1 and fibrinogen were significantly lower than those in other groups. Conclusions t-PA gene modified EPCs transplantation can effectively treat acute myocardial infarction in rats. Its specific therapeutic effect is related to improving cardiac function, promoting angiogenesis, inhibiting ventricular remodeling, inhibiting thrombosis or increasing thrombolysis.
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