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激光联合血管内皮生长因子基因促进缺血心肌血管再生的实验研究 被引量:2

Laser Combined with VEGF Gene Therapy on Myocardial Angiogenesis and Cardiac Function of Chronic Ischemic Porcine Myocardium: An Experimental Study
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摘要 目的 研究激光心肌血运重建 (TMLR)联合应用血管内皮生长因子 (VEGF)基因促进缺血心肌血管再生及提高心脏功能的效果。方法 选取中国实验小型猪 2 7只。在全麻下经左侧第 2肋间开胸 ,将Ameroid收缩环置于左旋支近段 6周 ,造成猪慢性缺血心肌模型。将模型猪随机分为 5组 :A组为缺血对照组 (n =5) ,B组为空白质粒对照组 (n =5) ,C组为TMLR治疗组 (n =5) ,D组为VEGF基因治疗组 (n =6) ,E组为TMLR +VEGF基因治疗组 (n =6)。采用高功率CO2 激光器对相应组猪心肌照射形成透壁性孔道 1 0个。VEGF治疗组将裸露VEGF1 65质粒蛋白 (PhcDNA3 1 ) 50 0 μg分别向 1 0个标记处心肌中层注射。 6周后处死动物后进行心肌血管密度测定。处死动物前采用 2D超声心动图仪检测左室射血分数 (LVEF)、室壁增厚率 (RT)和节段室壁运动指数 (WMSI)评价心室收缩功能 ,采用小剂量多巴酚丁胺负荷超声 (LDDSE)评价心功能储备。结果 治疗后 6周 ,C ,D ,E组猪缺血心肌的血管面积、周长和密度均明显多于A组和B组。其中E组在血管面积和周长方面明显优于C组 (P <0 0 5)和D组 (P <0 0 0 1 ) ,在血管密度 (>2 5μm)方面只明显优于D组 (P <0 0 0 1 ) ,而与C组差异无显著意义。C组总血管密度尤其是管径 >2 5μm的血管密度明显高于D组 (P Objective To study the effect of laser combined with and vascular endothelial growth factor (VEGF) gene therapy on myocardium in order to enhance angiogenesis and cardiac function of chronic ischemic myocardium achieved by transmyocardial laser revascularization (TMLR).Method Ameroid constrictor was placed on the proximal left circumflex artery in 27 pigs. After 6 weeks, the model animals were devided into 5 groups randomly: group A is the control group (n=5); group B is the plasmid group in which the empty plasmid vector was injected into the myocardium (n=5);group C is laser treated group in which about ten transmural channels were created in ischemic zone with carbon dioxide laser in every animal; group D is VEGF group that an expression plasmid containing the gene encoding VEGF 165 (500 μg) was administered directly into the myocardium at 10 sites in the circumflex distribution at (n=6); group E is TMLR+VEGF group, where about ten transmurul channels were created in ischemic zone with carbon dioxide laser and an expression plasmid containing the gene encoding VEGF 165 (500 μg) was administered directly into the myocardium at 10 sites as the same time and at the same area(n=7). The animals were sacrificed after 6 weeks. Sections from the ischemic zone were submitted for histologic analysis. The rate of wall thickening (RT) and, wall motion score index (WMSI)were detected by transthoracic 2D echocardiography. Results There was a significant increase in the area of vessels and total perimeter of vessels and number of vessels in the ischemic zone of the groups C, D and E in comparison with the control group A and group B. A significant increase in the area of vessels and total perimeter of vessels was seen in group E compared with the groups C(P<0 05) and D (P<0 001). There was a significant increase in the number of vessels(vessel diameter >25 μm) in group E compared with the group D but there were no different between group E and group C. A significant increase in the number of vessels (especial vessel diameter >25 μm) was seen in group C compared with the group D. There was significant improvement in RT and WMSI in groups C, D and E, but the difference was no significant in group E in comparison with groups C and D. Conclusions The cause of improvement of cardiac function resulted from the VEGF treatment enhanced by TMLR needs further research. TMLR could enhence the revascularization achieved by intramyocardial injection of the gene for VEGF.
出处 《中国激光医学杂志》 CAS CSCD 2002年第4期213-217,共5页 Chinese Journal of Laser Medicine & Surgery
基金 北京市科委资助项目 ( 955510 190 0 )
关键词 缺血心肌血管再生 实验研究 激光心肌血运重建 血管密度 基因治疗 血管内皮生长因子基因 心肌收缩 慢性缺血心肌 动物模型 Transmyocardial laser revascularization Number of vessels Gene therapy Vascular endothelial growth factor Myocardial contraction Chronic ischemic myocardium
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参考文献11

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