心室减负荷对缺血性心力衰竭MMPs/TIMPs的影响  

Effects of Ventricular Unloading on MMPs-TIMPs Expression in Rats with Post-myocardial Infarction Heart Failure

作　　者：刘永辉[1] 孟嘉天 孟自力[1] 李强[1] 郑浩[3] 王浩东 邸红芹[4] Liu Yonghui;Meng Jiatian;Meng Zili(Department of Cardiovascular Surgery,Hebei Chest Hospital,Hebei 050041,China)

机构地区：[1]河北省胸科医院心血管外科,石家庄050041 [2]河北省胸科医院放射科,石家庄050041 [3]河北省胸科医院超声科,石家庄050041 [4]河北省胸科医院检验科,石家庄050041

出　　处：《医学研究杂志》2021年第12期131-135,共5页Journal of Medical Research

摘　　要：目的通过大鼠缺血性心力衰竭心脏减负荷模型,探讨心室减负荷对缺血性心力衰竭心脏MMPs-TIMPs表达的影响。方法通过结扎冠状动脉前降支的方法,形成缺血性心力衰竭模型,随机分为两组,即减负荷组(n=14)与心力衰竭组(n=10),前者通过异位心脏移植的方法形成左心室减负荷模型;后者不进行心脏移植,另外8只大鼠作为空白对照组。2周后,测量左心室收缩压(LVSP)、左心室舒张末压(LVEDP)及最大压力上升及下降速度(±dP/dtmax)。用Western blot法、RT-PCR检测MMP-1、MMP-2、MMP-7、MMP-9、TIMP-1、TIMP-2、TIMP-3,以及TIMP-1/MMP-1的比值和TIMP-3/MMP-9、TIMP-2/MMP-2比值和TIMP-3/MMP-9比值。结果与对照组比较,心力衰竭组中的MMP-1、MMP-2和MMP-9基因表达明显增加;与心力衰竭组比较,在减负荷后,减负荷组的MMP-2和MMP-9基因表达水平下降明显,差异有统计学意义(P<0.05),TIMP-2和TIMP-3的基因表达明显升高,差异有统计学意义(P<0.05)。与心力衰竭组比较,TIMP-1/MMP-1的比值和TIMP-3/MMP-9均有明显升高(P<0.05);TIMP-2/MMP-2的比值升高更为明显(P<0.01)。与心力衰竭组比较,减负荷组的MMP-9和MMP-2的蛋白表达水平下降(P<0.05),TIMP-1和TIMP-3蛋白表达水平上升(P<0.05)。结论MMPs-TIMPs轴在心脏减负荷后心室重塑过程中发挥重要作用。对大鼠缺血性心肌病进行减负荷可以下调MMP-1、MMP-2和MMP-9,上调TIMP-1和TIMP-3,从而提高TIMPs与MMPs之比;在检测心脏细胞外基质方面,TIMPs/MMPs的比值较单个MMP或TIMP更加敏感。Objective To examine the role of matrix metalloproteinases(MMPs)-tissue inhibitors of metalloproteinases(TIMPs)axis in the process of recovery by ventricular unloading in rats with post-myocardial infarction heart failure model.Methods Myocardial infarction model was created with the coronary artery ligation in 29 adult lewis rats.The infarcted rats hearts were unloaded by heterotopic cardiac transplantation(n=14).Two weeks later,the function of normal and infarcted hearts with or without loading was evaluated by Langendorff perfusion model.The hearts were then harvested and prepared for the study of expression of MMPs and TIMPs.Results Developed pressure in the unloading group was higher than the loading group(P=0.0074).Unloading increased the ratio of TIMP-1/MMP-1(P<0.05),TIMP-2/MMP-2(P<0.01),TIMP-3/MMP-9(P<0.05).Although MMP-1,MMP-2,MMP-9 were downregulated(P<0.05),TIMP-2 and TIMP-3 upregulated(P<0.05),and MMP-7 and TIMP-1 was not affected significantly.Conclusion The infarcted cardiac function could be improved by unloading.It was attributed to downregulation of MMP-1,MMP-2 and MMP-9,and upregulation of TIMP-2 and TIMP-3.Furthermore,the ratio of TIMPs to MMPs was increased,which might be more sensitive than single MMPs or TIMPs for the judgment of myocardial matrix homeostasis.

关 键 词：心肌梗死 左心辅助装置 心力衰竭 心室重构 基质金属蛋白酶类 基质金属蛋白酶抑制剂 

分 类 号：R542.2[医药卫生—心血管疾病]