同种异体骨髓单个核细胞移植急性心肌梗死大鼠:心肌细胞凋亡及相关基因的表达  

Myocardial apoptosis and related gene expression in rats with acute myocardial infarction following bone marrow mononuclear cells transplantation

作　　者：张瑞成[1] 董念国[2] 梁凯[1] 侯剑峰[3] 武刚[3] 黄晓宇[3] 

机构地区：[1]河南省胸科医院心血管外科,河南省郑州市450008 [2]华中科技大学同济医学院附属协和医院心血管外科,湖北省武汉市430022 [3]郑州大学第二附属医院心血管外科,河南省郑州市450014

出　　处：《中国组织工程研究与临床康复》2009年第40期7898-7902,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:细胞凋亡增加所导致的进行性心肌细胞丢失是引起急性心肌梗死后充血性心力衰竭的主要原因之一,通过降低肿瘤坏死因子α浓度及Bax蛋白、PDCD5mRNA表达可以抑制急性心肌梗死后心肌细胞凋亡。目的:探讨同种异体骨髓单个核细胞移植对急性心肌梗死大鼠心肌细胞凋亡及相关基因表达的影响。设计、时间及地点:随机对照动物实验,于2006-01/11在华中科技大学附属协和医院完成。材料:体质量为(240±20)g的Wistar大鼠60只,随机分为假手术组、模型对照组、细胞移植组,20只/组。另取体质量为100～150g的Wistar大鼠60只用于制备骨髓单个核细胞。方法:模型对照组、细胞移植组大鼠结扎冠状动脉左前降支,建立急性心肌梗死模型;假手术组大鼠仅开胸,不结扎冠状动脉左前降支。造模后,细胞移植组大鼠在梗死心肌周围分4点于心外膜下植入骨髓单个核细胞悬液,每点100μL(107个细胞);假手术组、模型对照组同法注射等量DMEM培养基,培养4周。主要观察指标:血清及非梗死区心肌组织中肿瘤坏死因子α的水平,左室非梗死区心肌细胞凋亡指数、Bax蛋白和PDCD5mRNA的表达。结果:移植后4周,细胞移植组在发生凝固坏死的宿主心肌内可以看到局灶BrdU标记阳性的骨髓单个核细胞。与假手术组比较,移植后4周模型对照组、细胞移植组血清和心肌组织中肿瘤坏死因子α水平均显著升高(P<0.05),但细胞移植组升高幅度明显小于模型对照组(P<0.05)。与假手术组比较,模型对照组和细胞移植组左心室非梗死区心肌细胞凋亡指数、Bax蛋白和PDCD5mRNA(PDCD5/GAPDH)均明显升高(P<0.05),但细胞移植组升高幅度明显小于模型对照组(P<0.05)。结论:同种异体骨髓单个核细胞移植可以抑制大鼠心肌梗死后心肌细胞凋亡的发生,其机制可能与其抑制肿瘤坏死因子α的表达、降低Bax蛋白和PDCD5基因的促凋亡作用有关�BACKGROUND：The increased cell apoptosis results in cadiocyte loss,which is the main reason for congestive heart failure after acute myocardial infarction（AMI） . Myocardial apoptosis can be inhabited by decreasing tumor necrosis factor α（TNF-α） concentration,as well as the Bax protein,and PDCD5 mRNA expression. OBJECTIVE：To discuss the influence of allogenic bone marrow mononuclear cells（BM-MNCs） transplantation to the myocardial apoptosis of rats and related gene expression after AMI. DESIGN,TIME AND SETTING：The randomized control animal experiment was performed at the Affiliated Union Hospital Huazhong University of Science and Technology from January to November 2006. MATERIALS：Sixty Wistar rats,with body weight of（240±20） g,were randomly divided into sham surgery,model and transplantation groups,with 20 animals in each group. The other 60 Wistar rats weighted 100-150 g were prepared for BM-MNCs. METHODS：Rats in the model and transplantation groups were prepared for AMI models by ligating left anterior descending coronary artery. In the sham surgery group,rats’ chests were opened without ligating left anterior descending coronary artery. After model preparation,BM-MNCs suspension was implanted into infracted cardiac muscle via 4 points of epicardium with 100 μL per point in the transplantation group. The same volume DMEM was injected into rats of the sham surgery and model group. All rats were kept for 4 weeks. MAIN OUTCOME MEASURES：The index of myocardial apoptosis,the TNF-α content in blood serum and in the myocardium of the left ventricular non-infarcted area,the Bax albumin content and the PDCD5mRNA expression of left ventricular non-infarcted area were measured. RESULTS：The BrdU labeled positive BM-MNCs distributed focally in the myocardial infarction area of the transplantation group at 4 weeks after transplantation. Compared to the sham surgery group,the TNF-α content in blood serum and in the left ventricular non-infarcted myocardium in the control and transplantati

关 键 词：骨髓单个核细胞 移植 急性心肌梗死 细胞凋亡 基因 

分 类 号：R394.2[医药卫生—医学遗传学]