重组腺相关病毒介导CD151基因治疗心肌梗死后侧支循环形成  

rAAV-CD151 enhances collateral vascularization in swines with experimental acute myocardial infarction

作　　者：刘晓春[1] 左后娟[1] 刘正湘[1] 刘涛[1] 文莎[1] 刘少文[1] 汪道文[1] 张欣[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,武汉430030

出　　处：《中华急诊医学杂志》2009年第3期266-269,共4页Chinese Journal of Emergency Medicine

基　　金：基金项目：国家自然科学基金资助项目（30570728;30670856）

摘　　要：目的探讨重组腺相关病毒（rAAV）介导的CD151基因转染对小型猪心肌梗死模型后侧支循环重建的影响。方法中国实验用小型猪（清洁级，由华中农业大学种猪场提供）26头，随机分为：（1）正常对照组（n=4），健康小型猪，不进行任何手术处理；（2）rAAV-GFP组（n=7），结扎冠状动脉左前降支（left anterior descending，LAD）制备小型猪急性心肌梗死模型，心电监护显示Ⅰ、aVL导联ST段持续抬高20min为模型制备成功，同时，在左心室前壁梗死边缘区心肌分10点注射rAAV-GFP（1×10^11pfu／点）；（3）rAAV-CD151组（n=7），结扎LAD，左室前壁梗死边缘区心肌分10点注射rAAv-CD151；（4）rAAV-anti-CD151组（n=8），结扎LAD，左室前壁梗死边缘区心肌分10点注射rAAV-anti-CD151。8周后用Western Blot测定心肌组织CD151蛋白的表达，冠脉造影评价冠脉侧支循环形成情况。氯化三苯基四氮唑（TIC）染色显示心肌梗死面积。运用单因素方差分析进行统计学分析，以P〈0．05为差异具有统计学意义。结果与正常对照组和rAAV-GFP组比较，rAAV-CD151组心肌组织局部CD151蛋白表达增加（P〈0．05）。冠状动脉造影证实CD151基因转染明显促进闭塞动脉的侧支循环建立。rAAV-CD151组心肌梗死面积百分比明显小于rAAV-GFP组[（12．82±2．26）％vs．（23．14±2．83）％，P〈0．05]，rAAV-anti-CD151组心肌梗死面积百分比（32．52±3．47）％明显大于rAAV-GFP组和rAAV-CD151组（P〈0．05）。结论CD151基因转染可以明显促进小型猪急性心肌梗死后侧支循环的建立，减小心肌梗死面积。Objective To evaluate the delivery of recombinant adeno - associated vires （rAAV）-mediated CD151 gene in promoting neovascularization and coronary collateralization in swines after myocardial infarction. Method Twenty-six chinese minipigs （clean, provided by breeding pig farm of Huazhong Agricultural University） were randomly divided into four groups： （1） normal control group （n = 4）： swines without surgery. （2） rAAV- GFP group （ n = 7） ： The acute myocardial infarction models were produced in swines by ligating the left anterior descending coronary artery （LAD）. The success criteria of the models was that ST-segment elevations in leads Ⅰ and aVL maintained for 20 minutes. The rAAV-GFP was injected into the left ventricular anterior wall （divided into 10 points, 1 × 10^11 pfu/point）. （3） rAAV-CD151 group （ n = 7） ： The operation method was the same as rAAV- GFP group. The rAAV-CD151 was injected into the left ventricular anterior wall （divided into 10 points）. （4） rAAV-antiCD151 group （ n = 8） ： The operation method was the same as rAAV-GFP group. The rAAV-antiCD151 was injected into the left ventricular anterior wall （divided into 10 points）. Eight weeks after coronary artery ligation, the expression of CD151 was measured by western blot. Coronary angiography was done to evaluate collateral circulation of the infarct zone of myocardium. The infarct size was determined by staining with triphenyl-tetrazolium chloride （TFC）. Statistical analysis was carried out by using one-way analysis of variances. Results High level of CD151 protein expression was detected. Coronary angiography showed better collateral circulation in the rAAV- CD151 group. The percentage of infarct size was sinificanly lower in the rAAV-CD151 group （12.82 ± 2.26） % than that in the other two groups, and that was higher in rAAV - anti - CD151 group （32.52 ± 3.47） % than that in the rAAV-GFP group （23.14% ± 2.83 %, both P 〈 0.05）. Conclusions CD151 in vivo ge

关 键 词：急性心肌梗死模型 重组腺相关病毒介导 冠脉侧支循环形成 侧支循环重建 急性心肌梗死后 CD151 基因治疗 心肌梗死面积 

分 类 号：R542[医药卫生—心血管疾病]