CD151基因治疗改善小型猪心肌梗死后心功能的研究  

Experimental study of CD151 gene therapy on improving myocardial function in swines with myocardial infarction

作　　者：左后娟[1] 刘正湘[1] 刘晓春[2] 曾和松[1] 文莎[1] 刘涛[1] 汪道文[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 [2]华中科技大学同济医学院神经生物学系

出　　处：《中华老年医学杂志》2009年第9期755-759,共5页Chinese Journal of Geriatrics

摘　　要：目的研究重组腺相关病毒（rAAV）介导的CD151基因转染小型猪心肌梗死模型对心肌梗死后心功能的影响，以明确CD151体内促血管新生的作用。方法实验用小型猪分为4组：（1）正常对照组4只；（2）rAAV-含绿色荧光蛋白序列（GFP）组6只；（3）rAAV—CD151组6只；rAAV—antiCD151组6只。结扎猪冠状动脉左前降支建立心肌梗死模型。包装正义及反义CD151腺相关病毒，分点注射至梗死区及梗死周围心肌进行基因转染。基因转染8周行Western blot测定心肌组织CD151蛋白表达，氮13氨水（^13N～NH3）电子发射计算机断层显影（PET）评价心肌血流灌注，超声心动图检测心功能。结果CD151基因转染促进心肌组织局部CD151高表达。与rAAV—GFP组比较，基因转染8周时rAAVCD151组心肌缺损面积减小[（11．3±2．4）％与（21．1±2．6）％，t=-5．67，P〈0．01]，心功能各指标左心室射血分数[（65．7±4．6）％与（54．7±5．3）％，t=3．98，P〈0．051、左心室短轴缩短率[（36．0±2．9）％与（27．6±3．1）％，t=3．35，P〈O．051、左心室前侧壁的增厚率[（55．4±4．9）％与（36．8±7．8）％，t=3．34，P〈0．05]和室间隔的增厚率[（35．2±6．0）％与（26．7±4．4）％，t=9．27，P〈0．01]均增加，左心室前侧壁和室间隔的厚度亦增加（P〈0．05）。rAAV-antiCD151组各参数则低于rAAV—CD151组（均P〈0．05）。结论rAAV-CD151能有效转染小型猪心肌，增加缺血心肌血流灌注，减小梗死面积，明显增加心肌收缩力并改善心功能。Objective To investigate the effect of CD151 gene therapy on improving myocardial function in swines with myocardial infarction. Methods CD151, antisense CD151 and green fluorescent protein （GFP） were constructed into the recombinant adeno associated virus （rAAV）. Swines were divided into 4 groups： rAAV GFP group （6 swines）, rAAV-CD151 group （6 swines）, rAAV antiCD151 group （6 swines） and control group （6 swines）. The swines were performed with coronary artery ligation and intramuscularly injection with rAAV. Eight weeks after vector administration, western blot was used to detect gene expression of CD151. 13N-labeled NH3 positron emission tomography （PET） was used to evaluate myocardial perfusion. Echocardiography was used to assess myocardial function. Results Compared with the control group and the rAAV GFP group, the rAAV-CD151 group showed higher CD151 protein expression. Compared with the rAAV GFP group, the defect size of myocardium was decreased [（11.3±2.4）% vs. （21.1±2.6）%,t= -5.67,P〈0. 011 and left ventricular ejection fraction （EF）, left ventricular fractional shortening （FS）, the ratio of anterior lateral wall thickening （ΔALWT） and ratio of interventricuiar septum thickening （ΔIVST） were significantly improved in rAAV-CD151 group 8 weeks after vector administration （（65.7±4.6）% vs. （54.7±5.3）%, （36.0±2.9）% vs. （27.6±3.1）%,（55.4±4.9）% vs. （36.8±7.8）%, （35.2±6.0）% vs. （26.7±4.4）%, t=3.98, 3.35, 3.34, 9.27, all P〈 0.05]. The level of diastolie AI.WT and diastolic IVST was also increased in rAAV-CD151 group compared with rAAV--GFP group （P〈0.05 ）. Compared with rAAV CD151 group, parameters of myocardial function in rAAV antisense CD151 group were not improved （P〈0.05）. Conclusions rAAV CD151 can effectively transfect the myoeardium, increase the expression of CD151 protein, promote the blood perfusion of myocardium and improve the ventricular function after myoeardl.al infarction.

关 键 词：转染 基因疗法 心肌梗死 猪 

分 类 号：R686[医药卫生—骨科学]