血管内皮生长因子和一氧化氮对兔生理性缺血冠状动脉侧支血流量的影响

Effects of vascular endothelial growth factor and nitric oxide on coronary collateral blood flow during ischemic physical training

目的研究血管内皮生长因子（VEGF）和一氧化氮（NO）对兔生理性缺血训练（PIT）中侧支血流量的影响，为研究生理性缺血的侧支循环形成机制奠定基础。方法健康成年新西兰白兔55只，体重（2．0±0．5）kg。将水囊梗阻器安装在冠状动脉左室支，建立可控性心肌缺血模型，术中及术后实验兔死亡6只，另有2只因ECG无缺血改变未满足本实验的人选标准而剔除，余47只造模成功兔纳入实验。将47只兔按随机数字法分为假手术组（7只）、单纯心肌缺血组（7只）、单纯PIT组（11只）、VEGF抑制的PIT组（7只）、NO抑制的PIT组（9只）和VEGF—NO双抑制的PIT组（6只）。各组分别在造模时进行缺血刺激，并在刺激前后分别注射微球。处死前开胸时同样进行缺血刺激，且在刺激前后分别注射微球。实验终止时取左室前壁缺血心肌组织，采用微球技术检测缺血区相对侧支血流量。结果训练前造模时，各组缺血区心肌的相对侧支血流量基础值比较，差异无统计学意义（P〉0．05）。训练4周后，各组缺血心肌的相对侧支血流量较组内训练前均有明显增加（P〈0．01），且以单纯PIT组的侧支血流增加最多，由训练前的（39．23±9．39）％增加到（85．31±12．07）％；单纯心肌缺血组、单纯PIT组和NO抑制的PIT组心肌缺血区域心肌相对血流量分别与假手术组比较，差异有统计学意义（P〈0．05）；VEGF抑制的PIT组、NO抑制的PIT组及VEGF—NO双抑制的PIT组的心肌相对血流量均明显低于单纯PIT组（P〈0．05）；VEGF—NO双抑制的PIT组与NO抑制的PIT组的缺血心肌相对血流量组间比较，差异有统计学意义（P〈0．05），但与VEGF抑制的PIT组的组间差异无统计学意义（P〉0．05），且NO抑制的PIT组与VEGF抑制的PIT组的组间差异亦无统计学意义（P〉0．05）。单纯心肌缺血组和单纯PIT组分别与VEGF—NO双抑制的PIT组比较，组问差异均有统计学意义（P〈0．05）。结论PIT可以通过VEGF和NO增加远隔缺血心肌的侧支血流量，抑制VEGF和NO减弱缺血训练对侧支循环的促进作用；VEGF与NO均参与侧支循环的形成，且VEGF起主要作用。

Objective To explore the effects of vascular endothelial growth factor （VEGF） and nitric oxide （NO） on coronary collateral blood flow （CCBF） in a rabbit model of physical ischemie training （PIT） , and to provide a foundation for the study of the mechanism of collateral circulation formation in PIT. Methods Models of intermit- tent myocardial isehemia were established in 55 rabbits by installing a water balloon constrictor on the left ventricular coronary artery. The rabbits were then divided into a sham-operation group, a pure ischemia group, a PIT group, a PIT group with NO inhibition pretreatment, a PIT group with VEGF inhibition treatment, and a PIT group with both NO and VEGF inhibition pretreatment. Microspheres were injected at modeling and before sacrifice before and after ischemic stimulation. At the termination of the experiment the ischemie myocardial tissue of the left ventricular anterior wall was sampled, and then relative CCBF was measured using the microspheres. Results There was no significant difference among the 6 groups before training. After training prominent differences among the groups were observed, with the PIT group having the greatest increase in CCBF. CCBF in the pure ischemia group, the PIT group, and the PIT group with NO inhibition pretreatment were significantly higher than in the sham-operation group. Significant differences were also found between the PIT group and the three pretreatment groups. CCBF in the PIT group with NO pretreatment and VEGF inhibition was significantly different from that in the NO pretreatment group, while it was not found in the group with VEGF inhibition pretreatment. The CCBF in the group with VEGF inhibition pretreatment and the group with NO inhibition pretreatment was similar. Concluslons PIT can improve CCBF to the remote ischemic myocardium when combined with VEGF and NO pretreatment. Blocking VEGF or NO can reduce CCBF after training, and both VEGF and NO are involved in the formation of collateral circulation, with VEGF playing the major role.