hVEGF165腺相关病毒通过Bax和Bcl-2途径抑制细胞凋亡  

Cardiocyte Apoptosis Inhibited by rAAV-hVEGF_(165) through Bax and Bcl-2

作　　者：李曦铭[1] 王超[2] 王林[3] 韩瑞发[3] 刘立维[3] 丛洪良[1] 

机构地区：[1]天津市胸科医院,300051 [2]天津市南开医院 [3]天津医科大学第二医院

出　　处：《天津医药》2008年第12期954-957,共4页Tianjin Medical Journal

基　　金：天津自然科学基金资助项目(项目编号05YFJMJC12500)

摘　　要：目的:探讨直接心肌注射基因重组hVEGF165腺相关病毒(rAAV-hVEGF165)对急性心肌梗死大鼠心功能、心肌梗死面积、微血管数量、凋亡相关蛋白Bax和Bcl-2表达的影响。方法:81只SD大鼠根据注射药物的不同随机分成4组:假手术组15只,心肌梗死组(MI组)25只,生理盐水组(NS组)25只,血管内皮生长因子(VEGF)组16只。于注射4周后测定超声心动图参数、梗死面积、微血管数量、心肌细胞凋亡指数、心肌组织Bax和Bcl-2蛋白表达的变化。结果:VEGF组心肌梗死面积较MI组和NS组明显减小(P<0.05)。超声心动图提示VEGF组的射血分数要高于MI组和NS组(P<0.01)。血管计数显示VEGF组有更多的新生血管形成(P<0.01)。结论:直接心肌注射rAAV-hVEGF165能明显改善急性心肌梗死大鼠的心功能,缩小梗死面积,促进心肌内新血管的形成,减少心肌细胞凋亡,抑制Bax的表达,促进Bcl-2的表达。Objective： To determine the effects of intramyocardial injection of rAAV-hVEGF165 on cardiac function, infarct size,intramyocardial microvessels, and expression of Bax and Bcl-2 in a rat model of acutemyocardial infarction. Methods： Eighty-one male Sprague-Dawley rats weighing 260-300 g received a ligation of the left anterior decending artery to induce myocardial infarction （MI） under intraperitoneal anaesthesia, and 100 μL rAAV-hVEGF165 or saline was intramyocardially injected at three separated sites into the border zone of infarction. The models were randomly divided into four groups which included sham operation group （n=15）, saline group （n=25）, MI group （n=25）, and VEGF group （n=16）. Echocardio- graph data, infarct size, intramyocardial microvessels, apoptotic index, Bax and Bcl-2 expression in myocardium were measured 4 weeks after injection. Results：Three rats in sham operation group, thirteen rats in MI group, fifteen rats in saline group,and seven rats in VEGF group died during the experiment. The remaining 43 rats were included in the study. Infarct size in VEGF group were significantly lower than those in MI group and NS group （P 〈 0.05）. Echocardiograph data revealed the improvement of ejection fraction （EF%） in VEGF group was greater than those in MI group and NS group （P 〈 0.01）. There were more blood vessels in VEGF group （P 〈 0.01）. VEGF treatment significantly inhibited the expression of Bax, and increased expression of Bcl-2 in myocardium （P 〈 0.01）. Conclusion：Intramyocardial injection of rAAV-hVEGF165 is capable of sig-nificantly improving heart function, reducing infarct size, myocyte apoptosis and Bax expression, promoting myocardial neo-vascularization, and increasing Bcl-2 expression in a rat model of acute myocardial infarction.

关 键 词：心肌梗死 血管内皮生长因子类 基因疗法 腺病毒 人 原癌基因蛋白质类 基因 bcl-2细胞凋亡 

分 类 号：R394.8[医药卫生—医学遗传学] R575.202[医药卫生—基础医学]