摘要
背景:骨髓干细胞能够修复受损心肌,改善不利的心室重构及恶化的心功能,但细胞移植后对梗死心室重构影响的分子机制仍不清楚。目的:观察骨髓单个核细胞心肌移植后,心肌组织NF-κB、基质金属蛋白酶及其抑制因子表达的变化。设计、时间及地点:随机对照动物实验,于2006-07/2007-05在解放军总医院心血管外科实验动物中心和解放军军事医学科学院病原微生物生物安全国家重点实验室完成。材料:成年健康雄性杂种犬24只,随机分为急性心肌梗死对照组、急性心肌梗死移植组、陈旧心肌梗死对照组、陈旧心肌梗死移植组,6只/组。方法:急性心肌梗死对照组、急性心肌梗死移植组在冠状动脉左前降支主干结扎1h,观察缺血梗死区仍然呈暗红色,确认急性心肌梗死模型建立成功。陈旧心肌梗死对照组、陈旧心肌梗死移植组在移植前行超声心动图检查,证实左室前壁和心尖部可见节段性室壁运动异常,确认陈旧心肌梗死模型建立成功。Ficoll分离法获得犬自体骨髓单个核细胞悬液,急性心肌梗死移植组在造模后1h于梗死区及梗死边缘区分多点注射细胞悬液,每点注射0.5mL,(1～2)×107个细胞/mL;陈旧心肌梗死移植组于造模后4周开胸确认梗死区,同法行细胞移植。主要观察指标:RT-PCR法检测心肌组织基质金属蛋白酶及其抑制因子mRNA的表达,Western免疫印迹法检测心肌组织NF-κB的表达。结果:移植后6周与相应对照组比较,急性心肌梗死移植组、陈旧心肌梗死移植组的梗死区、梗死周围区基质金属蛋白酶2,9mRNA及NF-κB表达均显著降低(P<0.01),基质金属蛋白酶抑制因子1,2mRNA表达均显著升高(P<0.01)。结论:犬自体骨髓单个核细胞心肌移植可能通过抑制NF-κB活化,导致基质金属蛋白酶mRNA表达减少及其抑制因子mRNA表达增加,从而抑制梗死后心室重构过程。
BACKGROUND： Bone marrow stem cells can repair injured myocardium and improve adverse ventricle remodeling and aggravated heart function, but the molecular mechanism effects on infarcted ventricular remodeling following cell transplantation is still unclear. OBJECTIVE： To observe the changes in nuclear factor κB, matrix metalloproteinase and tissue inhibitor expression following bone marrow mononuclear cell transplantation. DESIGN, TIME AND SETTING： The randomized controlled animal experiment was performed at the Animal Experimental Center Department of Cardiovascular Surgery, General Hospital of Chinese PLA and State Key Laboratory of Pathogenic Microorganism Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences of Chinese PLA from July 2006 to May 2007. MATERIALS： A total of 24 healthy male hybrid adult dogs were equally randomized into four groups： acute myocardial infarction （AMI） control group, AMI transplantation group, old myocardial infarction （OMI） control group and OMI transplantation group. METHODS： Left anterior descending coronary artery was ligated for 1 hour in the AMI control and AMI transplantation groups. Dark red in the ischemic infarcted region indicated successful AMI model establishment. Before transplantation, dogs in the OMI control and OMI transplantation groups received echocardiography, which verified that abnormity of the segmental wall motion in the anterior wall and heart apex of the left ventricle and confirmed that successful OMI model establishment. Dog autologous bone marrow mononuclear cell suspension was obtained by the Ficoll separation. Cell suspension was injected into multiple sites in and around the infarcted region at 1 hour following establishment in the AMI transplantation group, 0.5 mL at each site, （1 -2） ×10^7 cells/mL. The chest was opened in the OMI transplantation group to define the infarcted region. Cell transplantation was performed by the same method. MAIN OUTCOME MEASURES： The mRNA expression
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第6期1113-1117,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
全军“十一五”重点课题资助项目(06G112)~~
