Int J Cardiol 2011 Oct;152 (1): 18-23. [IF:6.802]
CD34+ cell mobilization and upregulation of myocardial cytokines in a rabbit model of myocardial ischemia.
Zhao Q , Sun C , Xu X , Zhou J , Wu Y , Tian Y , Yuan Z , Liu Z .
Department of Cardiology, The First Affiliated Hospital of Medical College in Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. zhaoqingbin05@163.com
西安交通大学医学院第一附属医院心内科
Abstract
Studies have suggested that myocardial infarction may induce bone marrow stem cell mobilization and homing to the infarcted area, contributing to myocardial repair and tissue regeneration. Despite some encouraging results using stem cell therapy for myocardial regeneration in humans and animals, the mechanisms behind this activity remain unclear. In this study, we investigate stem cell mobilization and homing in ischemic myocardium, and investigate the involvement of cytokines TNFα and VEGF in this process. Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits. Immunohistochemistry analysis of ischemic myocardium showed the presence of VEGF and TNFα along with homing of CD34 positive (CD34+) cells to the region in the 7 days following surgery. During the same period, an increase in percentage of CD34+ cells in peripheral blood and in VEGF and TNFα mRNA expression in ischemic tissue was observed in animals that underwent partial LAD ligation. Terminal dUTP nick end-labeling (TUNEL) showed that cell apoptosis in the ischemic myocardium decreased between days 7 and 28 following surgery. None of these changes were observed in animals that underwent sham operation. In the early stages of myocardial ischemia, bone marrow stem cells are mobilized and home to ischemic myocardium with a concomitant increase in expression of cytokines VEGF and TNFα. Furthermore, cell apoptosis occurs in the ischemic myocardium, possibly due to the activity of TNFα which is thought to induce cardiomyocyte apoptosis.
摘要：
研究表明心肌梗塞可以诱导骨髓干细胞的动员和向梗塞部位的迁移，有助于心肌的修复和组织的再生。尽管在人体和动物体内使用干细胞疗法促使心肌再生取得了一些令人鼓舞的成果，但其具体的机制尚不明确。在这项研究中，主要研究了干细胞的动员和向缺血心肌部位的迁移，同时研究了在此过程中细胞因子TNFα和VEGF的作用。心肌梗塞的模型是使用雄性日本白兔，部分结扎左冠状动脉前降支制成。在手术后7天免疫组化技术分析发现在缺血部位发现CD34+细胞出现并伴有VEGF和TNFα的存在。在同一时期，发现外周血CD34+细胞比例增加且在部分左前降支结扎的动物外周血发现VEGF 和 TNFα mRNA表达的增高。末端标记法表明在术后7至28天这段时间内在缺血部位的细胞凋亡数目减少。这些变化些对比的动物试验中没有观察到。在心肌缺血的早期阶段，骨髓干细胞被动员并伴随VEGF 和 TNFα细胞因子表达增加向缺血心肌的部位迁移。此外，在缺血部位发生细胞凋亡可能由于TNFα的活性可以诱导心肌细胞凋亡。
