我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

经心内膜注射血管内皮生长因子基因治疗猪心肌缺血模型的远期效果观察

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第4期
页码:
486-490
栏目:
基础研究
出版日期:
2010-06-10

文章信息/Info

Title:
Long-term changes of heart function and ultrastructure after catheter-based transendocardial injection of naked DNA encoding vascular endothelial growth factor into ischemic porcine myocardium
作者:
赵志敬1; 郭文怡1; 吕安林1; 李伟杰1; 于铭2
第四军医大学西京医院:1.心血管内科,2.超声诊断科,陕西 西安 710033
Author(s):
ZHAO Zhi-jing1;  GUO Wen-yi1;  LV An-lin1;  LI Wei-jie1;  YU Ming2
1.Department of Cardiovasology, 2.Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, Xi'an 710033, Shaanxi, China
关键词:
血管内皮生长因子; 心肌缺血; 基因疗法; 猪
Keywords:
vascular endothelial growth factors;  myocardial ischemia;  gene therapy;  porcine
分类号:
R459.9
DOI:
-
文献标识码:
A
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（vascular endothelial growth factor，VEGF）基因治疗猪心肌缺血模型后，远期心功能以及局部超微结构的变化。方法: 将30只实验用小香猪均分为对照组（n=15）和治疗组（n=15）。以冠状动脉内球囊建立心肌缺血模型后，通过NOGA系统经心内膜将空质粒和pIRES2-EGFP-hVEGF165质粒分别直接注射至对照组和治疗组猪的缺血部位心肌内。在注射前及注射后1年，应用超声检测M型局部室壁的运动幅度和背向散射积分的心动周期变异（cardiac cycle variation of integrated backscatter，CVIB）和左心室射血分数（Left ventricular ejection fraction，LVEF）。1年后处死动物，通过检测Ⅷ因子的SABC染色法观察心肌组织中毛细血管生成的情况，并以透射电子显微镜观察局部超微结构的变化。 结果: 与对照组相比，治疗组术后1年时，M型局部室壁的运动幅度和CVIB、LVEF均显著增加（P<0.05）。检测Ⅷ因子的SABC染色法显示，对照组心肌内毛细血管数目为（13±5）个/HP；而治疗组为（38±5）个/HP（P<0.01）。透射电子显微镜观察发现，对照组梗死区残存心肌存在严重的心肌细胞萎缩，缺血区心肌肌丝出现不同程度纵向断裂，线粒体排列紊乱，时有肿胀、变性；而治疗组残存心肌仅轻度萎缩，缺血区心肌的结构较为正常。 结论: 猪心肌缺血模型经心内膜直接注射pIRES2-EGFP-hVEGF165基因后，远期可增加缺血心肌部位的血管新生，促进局部心肌细胞结构的恢复，从而改善心功能。
Abstract:
AIM: To investigate the long-term changes of heart function and ultrastructure after catheter-based transendocardial injection of naked DNA encoding vascular endothelial growth factor (VEGF) into ischemic porcine myocardium. METHODS: Thirty pigs were divided into control group (n=15) and VEGF group (n=15), and their left anterior descending coronary arteries were embolized by coronary artery balloon angioplasty. Constructed pIRES2-EGFP-hVEGF165 eukaryotic expression plasmid or blank plasmid was directly injected into the porcine ischemic myocardium through transendocardial injection catheter using NOGA system. Ultrasonography was used to detect the M-mode motion, cycle variation of integrated backscatter (CVIB) and left ventricular ejection fraction (LVEF). One year later, the animals were sacrificed to observe the capillary formation and ultrastructure in myocardial tissue by factor VIII strepto-avidin-biotin complex (SABC) staining and electronography, respectively. RESULTS: One year after the gene injection, M-mode motion, CVIB and LVEF showed a significant increase (P<0.05) and factor VIII SABC staining showed a significant increase in the number of capillaries ［(13±5)/HP vs. (38±5)/HP, P<0.01］ in the VEGF group compared with those in the control group. Electronography showed that myocardium atrophy (remaining myocardium in infarcted zone), myofilament fracture and mitochondrial degeneration (in ischemic zone) were heavier in the control group compared with those in the VEGF group. CONCLUSION: Transendocardial injection of naked DNA encoding VEGF into ischemic porcine myocardium increases capillary number, recovers local myocardial structure and increases heart function.

参考文献/References

［1］Koransky ML, Robbins RC, Blau HM. VEGF gene delivery for treatment of ischemic cardiovascular disease［J］. Trends Cardiovasc Med, 2002, 12(3):108-114.

［2］Henry TD, Annex BH, McKendall GR, et al. VIVA Investigators. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis［J］. Circulation, 2003, 107(10):1359-1365.

［3］Zhang D, Gai L, Fan R, et al. Efficacy and safety of therapeutic angiogenesis from direct myocardial administration of an adenoviral vector expressing vascular endothelial growth factor 165［J］. Chin Med J (Engl), 2002, 115(5):643-648.

［4］Yi F, Guo WY, Lü AL, et al. Vascular endothelial growth factor expressing esenchymal stem cells improves cardiac function in chronic myocardial infarction in pigs［J］. Chin Med J (Engl), 2006, 119(19):1664-1668.

［5］Ye L, Haider HKh, Tan R, et al. Angiomyogenesis using liposome based vascu1ar endothelial growth factor-165 transfection with skeletal myoblast for cardiac repair［J］. Biomaterials, 2008, 29(13):2125-2137.

［6］赵志敬,吕安林,贾国良，等. pIRES2-EGFP-hVEGF165真核表达载体的构建及在心肌细胞内的表达［J］. 第四军医大学学报, 2004, 25(12):1098-1100.

［7］李虎,贾国良,王海昌，等. 介入技术建立心肌梗死猪动物模型［J］. 心脏杂志, 2005, 17(4):334-336.

［8］李虎,秦涛,贾国良，等. 左心室电机械标测与造影对正常及梗死心肌评价的比较［J］. 第四军医大学学报, 2005, 26(18):1645-1648.

［9］ Jingjing L, Srinivasan B, Bian X, et al. Vascular endothelial growth factor is increased following coronary artery occlusion in the dog heart［J］. Mol Cell Biochem, 2000, 214(1-2):23-30.

［10］Post MJ, Laham R, Sellke FW, et al. Therapeutic angiogenesis in cardiology using protein formulations［J］. Cardiovasc Res, 2001, 49(3):522-531.

［11］Fuchs S, Kornowski R, Shiran A, et al. Electromechanical characterization of myocardial hibernation in a pig model［J］. Coronary Artery Dis, 1999, 10(3):195-198.

[12]Callans DJ, Ren JF, Michele J, et al. Electroanatomic left ventricular mapping in the porcine model of healed anterior myocardial infarction: correlation with intracardiac echocardiography and pathological analysis［J］. Circulation, 1999, 100(16):1744-1750.

[13]Wiggers H, Botker HE, Sogaard P, et al. Electromechanical mapping versus positron emission tomography and single photon emission computed tomography for the detection of myocardial viability in patients with ischemic cardiomyopathy［J］. J Am Coll Cardiol, 2003, 41(5):843-848.

备注/Memo

备注/Memo:
收稿日期：2010-02-24.基金项目：陕西省科学技术发展项目［2001K102G7(1)］ 通讯作者：赵志敬，讲师，主要从事冠心病机制及防治研究Email：zhaozhj@fmmu.edu.cn
更新日期/Last Update: 2010-05-20