重组腺相关病毒介导CD151转染心肌梗死小型猪促进心肌功能性血管形成  

Arteriogenesis induced by intramyocardial recombinant adeno-associated virus vector encoding human CD151 cDNA gene transfer in swines with coronary artery occlusion

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] 张欣[3] 

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 [3]美国田纳西大学分子科学部

出　　处：《中华心血管病杂志》2009年第6期537-541,共5页Chinese Journal of Cardiology

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

摘　　要：目的观察重组腺相关病毒（rAAV）介导的CD151基因转染促小型猪心肌梗死后心肌血管形成的有效性。方法结扎小型猪冠状动脉左前降支建立心肌梗死模型，梗死区及梗死周围心肌分别注射rAAV—CD151、rAAV—anti-CD151和rAAV-绿色荧光蛋白（rAAV-GFP）。8周后用Western blot分析心肌组织CD151蛋白表达，免疫组化检测心肌微血管密度和小动脉密度，用13^N-NH3电子发射计算机断层心脏显影（PET）评价心肌血流灌注。结果CD151基因转染促进心肌组织局部CD151高表达。rAAV—CD151组心肌微血管密度为（83．8±6．7）个／mm^2，明显高于正常对照组的（33．2±4．5）个／mm^2和rAAV—GFP组的（41．6±5．6）个／mm^2，均P〈0．05；rAAV—CD151组小动脉密度为（16．4±2．5）个／mm^2，也明显高于正常对照组的（6．6±2．3）个／mm^2和rAAV—GFP组（8．4±1．6）个／mm^2，均P〈0．05。rAAV—anti—CD151组心肌微血管密度和小动脉密度明显低于其他各组。13^N-NH3PET心肌血流灌注显像示rAAV—CD151组缺血区心肌血流灌注明显增加，rAAV-anti-CD151组血流灌注减少。结论CD151基因转染能增加小型猪局部心肌组织的CD151表达，明显增加缺血心肌微血管和小动脉的生成，并显著增加心肌血流灌注。Objective To investigate the efficacy of CD151 gene delivery in promoting blood perfusion in swines after myocardial infarction. Methods Swines received coronary artery ligation and intramyocardial injection with rAAV-CD151, rAAV-anti-CD151 or rAAV-GFP. Eight weeks after vector injection, Western blot, immunostaining and 13^N-labeled NH3 PET were performed to detect gene expression and biological effects of various treatments. Results High level of CD151 protein expression was detected in the rAAV-CD151 group. The capillary density in the rAAV-CD151 group [ （83.8 ± 6. 7）n/mm^2] was significantly higher than that in the control group [ （33.2 ±4.5 ） n/mm^2 ] and rAAV-GFP group [ （41.6 ± 5.6 ）n/mm^2] （ all P〈0. 05） ; the arteriole density in the rAAV-CD151 group [ （16. 4 ±2. 5）n/mm^2] was also higher than that in the control group [ （6. 6 ± 2. 3 ） n/mm^2 ] and the rAAV-GFP group [ （ 8.4 ± 1.6 ） n/mm^2 ] （ all P 〈 0. 05 ）. However, the lowest capillary density and arteriole density were evidenced in rAAV-anti-CD151 group. Myocardial blood perfusion was significantly increased in rAAV-CD151 group and significantly reduced in rAAV-anti-CD15l group （all P 〈 0.05 vs. control ） . Conclusion Intramyocardial injection of rAAV-CD151 could enhance the myocardial express of CD151 protein, increase capillary and arteriole densities and improve blood perfusion in swine with myocardial infarction.

关 键 词：心肌梗死 新生血管化 生理性 腺相关病毒 

分 类 号：R686[医药卫生—骨科学]