TK-1和TIMP-1过表达对大鼠心肌梗死后心室重塑的影响  

Effects of TK-1 and TIMP-1 Over-expression on Ventricular Remodeling after Myocardial Infarction in Rats

作　　者：郑熙[1] 余惠珍[2] 高洁[3] 朱鹏立 ZHENG Xi;YU Hui-zhen;GAO Jie;ZHU Peng-li(The Third Internal Medicine-Cardiovascular Department,Fujian Provincial Hospital,Fujian 350001,China;Department of Cardiology,Fujian Provincial Hospital South Branch,Fujian 350028,China;Key Laboratory of Geriatrics,Provincial Clinical Medical College of Fujian Medical University,Fujian 350001,China;Fujian Institute of Clinical Geriatrics,Fujian 350001,China)

机构地区：[1]福建省立医院心血管内三科,福建福州350001 [2]福建省立医院南院内科,福建福州350028 [3]福建医科大学省立临床医学院老年医学研究室,福建福州350001 [4]福建省临床老年病研究所,福建福州350001

出　　处：《中山大学学报（医学科学版）》2020年第3期403-414,共12页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81670258,81873515);福建省自然科学基金(2017J01247)。

摘　　要：【目的】探讨重组腺病毒介导的人TK-1和TIMP-1基因过表达对大鼠心肌梗死后的左室(LV)功能、炎症因子表达的影响及其机制。【方法】通过结扎Sprague-Dawley雄性大鼠冠脉左前降支诱导心肌梗死模型。观察假手术组(10只)、生理盐水组(13只)、对照病毒组(13只)、TK-1组(13只)、TIMP-1组(13只)、联合基因组(13只)的大鼠术后的心功能参数改变、心肌梗死面积、及各组大鼠基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、核因子-κB(NF-κB)和巨噬细胞迁移抑制因子(MIF)的表达水平。【结果】与假手术组相比,对照病毒组大鼠的各项心功能参数(左室舒张期内径LVIDd、左室收缩期内径LVIDs、短轴缩短率FS、射血分数EF)差(P<0.01),心肌梗死面积大(P<0.01),心肌细胞凋亡指数高(P<0.01),各炎症因子(NF-κB、MIF、MMP-2、MMP-9)的表达水平上升(P<0.01)。与对照病毒组相比,单基因组或联合基因组的心功能改善明显;心肌梗死的面积明显减少;心肌细胞凋亡指数显著下降;炎症因子的表达明显下降。相比于单基因组,联合基因组各项指标改善更显著。【结论】hTK-1或hTIMP-1单基因过表达可改善大鼠心肌梗死后的心功能,抑制炎症因子表达与心肌细胞凋亡,联合基因过表达(hTK-1和hTIMP-1)呈协同效应、改善更显著,可能的机制为hTK-1或hTIMP-1均可部分抑制MIF/NF-κB/MMP-2/9炎症信号通路。【Objective】To investigate the effects of recombinant adenovirus mediated overexpression of human TK-1 or TIMP-1 gene on left ventricular function and expression of inflammatory factors after myocardial infarction in rats and its mechanism.【Methods】Myocardial infarction model was induced by ligation of left anterior descending coronary artery in Sprague Dawley male rats.We observed the changes of cardiac function parameters,myocardial infarction area,matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),nuclear factor kappa B(NF-κB)and MIF in sham operation group(10 rats),saline group(13 rats),control virus group(13 rats),TK-1 group(13 rats),TIMP-1 group(13 rats)and combined genome group(13 rats).【Results】Compared with the sham operation group,the LV function parameters(left ventricular diastolic diameter,left ventricular systolic diameter,shortening rate of short axis,ejec?tion fraction)of the control group were worse(P<0.01),myocardial infarction area was larger(P<0.01),myocardial apoptosis index was higher(P<0.01),and the expression level of inflammatory factors(NF-κB,MIF,MMP-2,MMP-9)was significantly higher(P<0.01).Compared with the control virus group,the LV function of single genome or combined genome improved significantly;the area of myocardial infarction was decreased significantly;the apoptosis index of myocardial cells was decreased significantly;and the expression of inflammatory factors was decreased significantly.Compared with single genome,the indexes of combined genome were improved significantly.【Conclusions】The overex?pression of hTK-1 or hTIMP-1 alone can improve the cardiac function after myocardial infarction,and inhibit the expres?sion of inflammatory factors and apoptosis of cardiomyocytes.The combined gene overexpression(hTK-1 and hTIMP-1)has a synergistic effect and more significant improvement.The possible mechanism is that either hTK-1 or hTIMP-1 could partially inhibit the MIF/NF-κB/MMP-2/9 inflammatory signaling pathway.

关 键 词：组织激肽释放酶1 基质金属蛋白酶抑制物1 巨噬细胞迁移抑制因子 核转录因子ΚB 心肌梗死 心室重塑 

分 类 号：R541.4[医药卫生—心血管疾病]