摘要
目的探讨经心内膜心肌内直接注射血管内皮生长因子(VEGF)基因治疗猪心肌缺血后的远期心脏电机械活动及心功能改善情况。方法30只实验用小香猪随机均分为对照组(n=15)和治疗组(n=15)。建立心肌缺血模型后,通过NOGA系统经心内膜分别将空载质粒pIRES2-EGFP及质粒pIRES2-EGFP-hVEGF165直接注射至对照组或治疗组缺血部位心肌内。在注射前及注射后1年,分别应用左心室电机械标测(LVEMM)监测局段线性缩短率(LLS)和单极电压(UpV),并用超声监测M型局部室壁运动幅度和背向散射积分的心动周期变异(CVIB)、左心室射血分数(LVEF)。1年后处死动物,组织学切片观察心肌组织中毛细血管生成情况。结果LVEMM监测显示,注射后1年治疗组LLS显著高于注射前及对照组(P<0.05),而UpV与注射前及对照组比较无显著差异(P>0.05);超声监测显示,治疗组注射后1年的局部室壁运动幅度和CVIB、LVEF均显著高于对照组(P<0.05)。组织学检查显示,治疗组心肌内毛细血管数目(38.1±4.8/HP)显著高于对照组(13.2±5.1/HP,P<0.01)。结论经心内膜直接注射pIRES2-EGFP-hVEGF165可增加猪远期缺血心肌部位的血管新生,改善局部电机械特性,从而改善心功能。
Objective To investigate the long-term efficacy of transendocardial injection of vascular endothelial growth factor (VEGF) into ischemic porcine myocardium.Methods Thirty pigs were divided into two groups:control group and treatment group (15 each).A angioplasty balloon was used to occlude the left anterior descending coronary arteries of the animals to reproduce a porcine myocardial ischemic model.Blank plasmid (control group) or constructed pIRES2-EGFP-hVEGF165 eukaryotic expression plasmid (treatment group) was directly injected into the ischemic myocardium through an transendocardial injection catheter of NOGA system,respectively.Before and one year after injection,left ventricular electromechanical mapping (LVEMM) was used to detect local linear shortening (LLS) and unipolar potential (UpV);M-mode local wall motion,cycle variation of integrated backscatter (CVIB) and left ventricular ejection fraction (LVEF) were detected by ultrasonagraphy.One year later,the animals were sacrificed for the observation of the capillary formation in myocardial tissue with immunohistochemical staining.Results One year after injection,as compared with that of control group,local linear shortening (LLS) showed a significant increase (P0.05),unipolar potential (UpV) showed no significant change in treatment group (P0.05),and ultrasonagraphy showed better heart function in the treatment group (P0.05).Histological study showed a significant increase in the number of capillaries in treatment group [(38.1±4.8)/HP] compared with control group [(13.2±5.1)/HP,P0.01].Conclusion Transendocardial injection of naked DNA encoding VEGF into ischemic porcine myocardium may increase the capillary number,improve the local electromechanical characteristics and improve the heart function.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2010年第4期384-386,390,共4页
Medical Journal of Chinese People's Liberation Army
基金
陕西省科学技术发展项目[2001K102G7(1)]
关键词
血管内皮生长因子类
心肌缺血
基因疗法
内皮
血管
vascular endothelial growth factors
myocardial ischemia
gene therapy
endothelium
vascular