摘要
目的观察心肌内注射转染血管生长素基因对心肌梗死大鼠梗死面积、非梗死区心肌肥厚以及心功能的影响。方法成年雄性Wistar大鼠,随机分为假手术组、MI-rAAV-lacZ组和MI-rAAV-ANG组。后2组以直视下结扎冠脉左前降支的方法建立心肌梗死模型,然后取rAAV-lacZ或rAAV-ANG载体在梗死区周围多点注射。1周和4周后分别测量心肌梗死面积。4周后超声心动图测量左室后壁厚度和左室射血分数(LVEF),颈动脉插管测量有创左室血流动力学指标。大鼠处死后左室称重,计算左室重量与体重比值。Western blot方法检测大鼠左室心肌组织ANG蛋白表达水平。结果左前降支结扎1周时,MI-rAAV-lacZ组和MI-rAAV-ANG组大鼠梗死面积无明显差异。4周后,MI-rAAV-lacZ组大鼠梗死面积显著大于1周时,亦显著大于MI-rAAV-ANG组4周时。与假手术组相比,MI-rAAV-lacZ组大鼠左室后壁肥厚、左室重量增加。4周后,与MI-rAAV-lacZ组相比,MI-rAAV-ANG组左室心肌ANG蛋白表达显著增加,梗死区扩展程度减轻,后壁厚度和左室重量恢复至假手术组水平。与假手术组相比,所有心肌梗死大鼠4周后均表现出显著的左室功能不全,rAAV-ANG转染显著改善心肌梗死大鼠左室功能。结论心肌内注射方式转染rAAV-ANG载体显著上调心肌梗死大鼠左室心肌ANG蛋白表达水平,抑制梗死区扩展和非梗死区肥厚,部分抑制心功能不全的发生发展。
Objective To observe the effects of angiogenin(ANG) gene transfection on the infarction area,hepertrophy of noninfarction area,and cardiac function in rats with myocardial infarcion(MI). Methods Adult male Wistar rats were randomly divided into 3 groups: sham-operation group,MI-rAAV-lacZ group and MI-rAAVANG group.In the other two groups,left anterior descending coronary artery was ligated to generate MI model,then rAAV-lacZ or rAAV-ANG was injected intramyocardially around the infaction area.One week or 4 weeks after the coronary artery ligation and gene transfection,infarction area was detected with echocardiography.Four weeks later,echocardiography was performed to detect posterior wall thickness and left ventricular ejection fraction,hemodynamic measurement was performed to evaluate left ventricular function.Left ventricle was weighed and left ventricular weight to body weight ratio was calculated.Myocardium ANG protein level was detected with Western blot. Results No difference of MI area was observed between MI-rAAV-lacZ group and MI-rAAV-ANG group one week after coronary artery ligation.Four weeks after the ligation,MI area was markedly increased in the MI-rAAV-lacZ group.Compared with sham-operation group,posterior wall thickness and left ventricular weight increased in the MI-rAAV-lacZ group.Compared with MI-rAAV-lacZ group,myocardium ANG protein level was significantly increased,infarction extension attenuated,posterior wall thickness and left ventricular weight restored in MI-rAAV-ANG group.Compared with sham-operation group,decreased LVEF,LVSP,+dp/dtmax,-dp/dtmax and increased LVEDP were observed in all MI rats,including MI-rAAV-lacZ group and MI-rAAV-ANG group.Compared with MI-rAAV-lacZ group,cardiac function improved markedly in MI-rAAV-ANG group.Conclusion rAAV-ANG transfection by intramyocardial injection upregulats myocardium ANG protein level,inhibits infarction extension,hypertrophy of noninfarction area,partially prevent the development of cardiac dysfunction in rats with MI.
出处
《河南职工医学院学报》
2007年第3期193-198,共6页
Journal of Henan Medical College For Staff and Workers
关键词
心肌
血管生长素
大鼠
myocardial infarction
angiogenin
rat
