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背景:细胞移植治疗心肌梗死为重建受损心肌带来希望,但移植后的细胞分化以及细胞移植能否长期持久地改善心脏功能等问题均不明确。目的:观察骨髓单个核细胞经冠状动脉移植入犬梗死心肌后,在心肌组织的分布、分化情况以及对心功能的影响。设计、时间及地点:随机对照动物实验,于2007-07/2008-03在泰达国际心血管病医院完成。材料:成年杂种犬16只,随机分为细胞移植组10只、模型对照组6只。方法:细胞移植组于髂前上嵴或髂后上棘穿刺抽取骨髓,经Ficoll密度梯度离心法分离获取骨髓单个核细胞,行CM-DiI标记。两组犬均结扎冠状动脉前降支建立急性心肌梗死模型,于心肌梗死后2h,细胞移植组向心肌梗死区注射骨髓单个核细胞悬液1mL(3×107~1×108个细胞),模型对照组注射等量生理盐水。主要观察指标:血流动力学指标及超声心动图指标的变化,免疫荧光染色观察骨髓单个核细胞在心脏的迁移、分布及分化结果:与模型对照组比较,细胞移植后6周细胞移植组血流动力学指标左室舒张末压显著降低(P<0.01),心排出量明显升高(P<0.05);超声心动图指标左室收缩末容积、左室舒张末容积均得到显著改善(P<0.01),射血分数、每搏输出量亦明显改善(P<0.05)。自体骨髓单个核细胞经冠状动脉移植后,可分布于心肌梗死区及梗死周边区,并表达肌球蛋白重链、连接蛋白43。结论:自体骨髓单个核细胞经冠状动脉移植后可分化为心肌样细胞,改善急性心肌梗死后的心功能。
BACKGROUND: Cell transplantation for myocardial infarction provides hope for the reconstruction of damaged myocardium. However, the problems of cell differentiation after transplantation and the long-term and long-lasting improvement of cardiac function after transplantation are not clear. OBJECTIVE: To observe the distribution and differentiation of bone marrow mononuclear cells (CMBs) in cardiac muscle after coronary artery transplantation into myocardial infarcted myocardium and its influence on cardiac function. DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed at TEDA International Cardiovascular Hospital from 2007-07 / 2008-03. MATERIALS: Sixteen adult mongrel dogs were randomly divided into 10 cell transplantation groups and 6 model control groups. Methods: Bone marrow was collected from the anterior superior iliac crest or iliac superior spine by cell transplantation group. The bone marrow mononuclear cells were isolated by Ficoll density gradient centrifugation and labeled with CM-DiI. The model of acute myocardial infarction was established by ligation of the anterior descending coronary artery in both groups. 2 h after myocardial infarction, 1 mL (3 × 107 ~ 1 × 108 cells) of bone marrow mononuclear cell suspension was injected into the myocardial infarction area in the cell transplantation group, The control group was injected with normal saline. MAIN OUTCOME MEASURES: Changes of hemodynamics and echocardiographic parameters. Immunofluorescence staining was used to observe the migration, distribution and differentiation of bone marrow mononuclear cells in the heart. Results: Compared with the model control group, the blood transfusion group at 6 weeks after transplantation Left ventricular end-diastolic pressure was significantly decreased (P <0.01) and cardiac output was significantly increased (P <0.05). Echocardiographic parameters of left ventricular end-diastolic volume and left ventricular end-diastolic volume were significantly improved (P <0.01). The ejection fraction and stroke volume were also significantly improved (P <0.05). Autologous bone marrow mononuclear cells after coronary artery transplantation, can be distributed in the myocardial infarction and infarct peripheral areas, and express myosin heavy chain, connexin43. CONCLUSION: Autologous bone marrow mononuclear cells can differentiate into cardiomyocyte after coronary artery transplantation and improve cardiac function after acute myocardial infarction.