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利用斑点追踪超声心动图得出的应变值评估间充质干细胞联合碱性成纤维细胞生长因子逆行冠状动脉静脉注射在犬心肌梗死中的作用

Assessment of Retrograde Coronary Venous Infusion of Mesenchymal Stem Cells Combined with Basic Fibroblast Growth Factor in Canine Myocardial Infarction Using Strain Values Derived from Speckle-Tracking Echocardiography.

作者信息

Sun Qi-Wei, Zhen Lei, Wang Qin, Sun Yan, Yang Jiao, Li Yi-Jia, Li Rong-Juan, Ma Ning, Li Zhi-An, Wang Lu-Ya, Nie Shao-Ping, Yang Ya

机构信息

Ultrasound Department, Beijing AnZhen Hospital Affiliated with Capital Medical University, Beijing, China.

Emergency & Critical Care Center of Beijing AnZhen Hospital Affiliated with Capital Medical University, Beijing, China.

出版信息

Ultrasound Med Biol. 2016 Jan;42(1):272-81. doi: 10.1016/j.ultrasmedbio.2015.09.010. Epub 2015 Oct 29.

Abstract

Speckle-tracking echocardiography was used to assess retrograde coronary venous infusion of mesenchymal stem cells (MSCs) combined with basic fibroblast growth factor (bFGF) in a canine model of acute myocardial infarction (AMI). AMI was induced by ligation of the left anterior descending coronary artery. Coronary venous retroperfusion was performed at 1 wk after AMI. Twenty-eight animals were randomized into four groups: saline, bFGF+saline, saline+MSCs and bFGF+MSCs. Echocardiography was performed before AMI, at 7 d post-AMI and 40 d after retroperfusion. Apoptotic cardiomyocytes in the border zone of the ischemic region were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Vascular endothelial growth factor and factor VIII concentrations were measured by western blotting. The left ventricular end-systolic volume increased significantly, whereas the left ventricular ejection fraction and global and segmental strain values decreased significantly after AMI. After retroperfusion, the strain values of the infarct zone, but not conventional echocardiographic parameters, were significantly different between control and bFGF+MSC groups. Cardiomyocyte apoptosis decreased, whereas vascular endothelial growth factor and factor VIII concentrations were higher in the bFGF+MSC, bFGF and MSC groups. Cardiomyocyte apoptosis was well correlated with the strain values. Although retrograde coronary venous infusion of bFGF and MSCs promoted neo-vascularization of the infarcted myocardium and inhibited apoptosis, there was only a slight strain improvement without a substantial increase in global cardiac functions.

摘要

采用斑点追踪超声心动图评估在犬急性心肌梗死(AMI)模型中介导间充质干细胞(MSCs)与碱性成纤维细胞生长因子(bFGF)逆行冠状动脉静脉输注的情况。通过结扎左冠状动脉前降支诱导急性心肌梗死。在急性心肌梗死后1周进行冠状动脉静脉逆行灌注。28只动物随机分为四组:生理盐水组、bFGF+生理盐水组、生理盐水+间充质干细胞组和bFGF+间充质干细胞组。在急性心肌梗死前、急性心肌梗死后7天和再灌注后40天进行超声心动图检查。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法评估缺血区域边缘区的凋亡心肌细胞。通过蛋白质印迹法测量血管内皮生长因子和因子VIII的浓度。急性心肌梗死后,左心室收缩末期容积显著增加,而左心室射血分数以及整体和节段应变值显著降低。再灌注后,梗死区的应变值在对照组和bFGF+间充质干细胞组之间存在显著差异,但传统超声心动图参数无差异。bFGF+间充质干细胞组、bFGF组和间充质干细胞组中心肌细胞凋亡减少,而血管内皮生长因子和因子VIII浓度较高。心肌细胞凋亡与应变值密切相关。虽然bFGF和间充质干细胞逆行冠状动脉静脉输注促进了梗死心肌的新生血管形成并抑制了细胞凋亡,但整体心功能仅有轻微改善,并未显著增加。

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