心肌注射碱性成纤维细胞生长因子促进犬侧支血管形成的实验研究

Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor in a canine model of acute myocardial infarction

目的 评价在犬急性心肌梗死模型中 ,心肌内注射碱性成纤维细胞生长因子 (bFGF)对心肌局部血流量及侧支血管形成的影响。方法 17条杂种犬 ,结扎第一、第二对角支和第一、第二钝缘支造成急性心肌梗死模型。冠状动脉结扎 2 0min后 ,治疗组 (n =9)在梗死边缘区心肌 5点注射2 0 0 μgbFGF ,对照组 (n =8)以相同的方法注射生理盐水 2 0 0 μl。在冠状动脉结扎之前、结扎即刻、结扎后 3h、7d及 2 8d使用非放射性彩色微粒子测量心肌局部血流量。试验终点观察侧支血管密度变化。结果 与对照组相比 ,治疗组心肌注射 2 0 0 μgbFGF后 ,梗死区心外膜心肌局部血流量明显增加 :冠状动脉结扎 3h治疗组心肌血流量为 (36 4 0± 2 0 4 ) % ,对照组为 (32 32± 3 0 7) % ,P <0 0 5 ;7d后治疗组为 (5 6 30± 3 4 9) % ,对照组为 (35 6 8± 1 6 2 ) % ,P <0 0 1;2 8d分别为 (70 6 2±3 17) % ,(46 2 0± 2 5 8) % ,P <0 0 1。与之相似 ,治疗组梗死边缘区心外膜心肌血流量也明显增加 :冠状动脉结扎 7d治疗组为 (6 8 0 6± 2 6 9) % ,对照组为 (5 3 94± 2 2 7) % ,P <0 0 1;2 8d治疗组为(79 74± 4 6 1) % ,对照组为 (6 1 84± 4 5 2 ) % ,P <0 0 1。与对照组相比 ,治疗组梗死区血管密度 :治疗组为 (7

Objective To evaluate the effects of intramyocardial administration of basic fibroblast growth factor (bFGF) on myocardial blood flow and angiogenesis in a canine acute myocardial infarction model. Methods Myocardial infarction was induced in 17 dogs by ligation of the first, second diagonal branches of left anterior descending (LAD) and the first, second obtuse marginal branches of LCX. 200 μg of human recombinant bFGF in 0.2 ml of saline was injected into the infarct border zone 20 minutes after coronary occlusion in 9 dogs, whereas 200 μl saline was used in 8 control dogs. Myocardial blood flow, which was expressed as percentage of normal, was determined with non-radioactive colored microspheres before and immediately after coronary ligation, 3 hours, 7 days and 28 days after treatment. Angiogenesis was determined at the end of the whole study. Results Compared with control group, treatment with 200 μg bFGF significantly increased the epicardial blood flow in the infracted zone [(36.40±2.04)% vs (32.32±3.07)% 3 hours after coronary ligation, P <0.05; (56.30±3.49)% vs (35.68±1.62)% 7 days after coronary ligation, P <0.01; and (70.62±3.17)% vs (46.20±2.58)% 28 days after coronary ligation, P <0.01, respectively]. bFGF also significantly increased the epicardial blood flow in the border zone[(68.06±2.69)% vs (53.94±2.27)% 7 days after coronary ligation, P <0.01; (79.74±4.61) % vs (61.84±4.52) % 28 days after coronary ligation, P <0.01, respectively]. bFGF increased the vessel density in the infarcted zone (7.24 ±1.89 vessels/mm 2 vs 4.07±1.89 vessels/mm 2, P <0.05) and infarcted border zone(14.48±4.69 vessels/mm 2 vs 8.15±3.43 vessels/mm 2, P <0.05). Conclusion The current study shows that intramyocardial administration of bFGF increases the regional myocardial blood flow and promotes myocardial collateral vessel formation in the canine acute myocardial infarction model.