兔骨骼肌生理性缺血对缺氧诱导因子-1α的表达和血管内皮生长因子释放的影响

关键词：血管内皮生长因子  缺氧诱导因子-1α  心肌缺血再灌注

Keywords:vascular endothelial growth factor  hypoxia-inducible factor-1α  myocardial ischemia/reperfusion

摘要：

      摘要 目的：验证生理性骨骼肌缺血训练上调血管内皮生长因子（vascular endothelial growth factor, VEFG）的表达与骨骼肌局部缺血产生的缺氧诱导因子（hypoxia inducible factor-1ɑ,HIF-1α）有关，进一步探讨VEFG的上游调控机制。 方法：成年雄性新西兰大白兔随机分成：①心肌缺血再灌注组（I/R组，n=6）；②假手术组（Sham组，n=6），步骤同I/R组，但仅穿线，不牵拉；③骨骼肌缺血+I/R组（n=6），在心肌I/R之前先实施反复骨骼肌缺血/再灌注。ELISA检测外周血中VEGF的表达，Western blot检测肢体肌肉处HIF-1α的表达。 结果：与Sham组相比，心肌I/R组及骨骼肌缺血+I/R组都可促进外周血中VEGF的释放，且后者的作用更显著，骨骼肌缺血+I/R组与心肌I/R组相比对VEGF的释放有显著性差异（P＜0.05）；与Sham相比，骨骼肌缺血+I/R组可以上调HIF-1α的表达（P＜0.05），而I/R组相对于Sham组HIF-1α的表达无明显的变化（P＞0.05），且骨骼肌缺血+I/R组与I/R组相比对HIF-1α的表达有显著性差异（P＜0.05）。 结论：骨骼肌生理性缺血可导致局部HIF-1α的高表达，同时对应着外周VEFG的表达增高，且较单纯的心肌缺血水平更高，推测外周VEGF的高表达与缺血局部骨骼肌释放HIF-1α有关。

Abstract:

      Abstract Objective: To verify the underlying mechanism that repeated physiological skeletal muscle ischemia training can promote the expression of vascular endothelial growth factor (VEGF) via upregulating hypoxia inducible factor-1ɑ (HIF-1α) in rabbit ischemic skeletal muscle. Method: Clean level male white rabbits of New Zealand, weight 2.2—2.5kg, were randomly divided into the following groups: Sham (n=6), myocardial ischemia/reperfusion (I/R, n=6), skeletal muscle ischemia+I/R (n=6). The right hind legs of rabbit were ligated to block femoral artery blood by manual tourniquet ring, till the pulse of femoral artery disappeared, lasting for five minutes, and then loosened for five minutes, four times cycles. Subsequently, we collected the serum and the limb muscle to detect the release of VEGF and the expression of HIF-1α, respectively. Result: Myocardial I/R and skeletal muscle ischemia+I/R could promote the expressions of VEGF compared with shame group (P＜0.05), and VEGF was more obvious in skeletal muscle ischemia+I/R group than those in the I/R group (P＜0.05). The expression of HIF-1α had no significant difference between shame group and I/R group (P＞0.05).However, the level of HIF-1α was increased in skeletal muscle ischemia+I/R compared with I/R group (P＜0.05). Conclusion: Skeletal muscle ischemia can promote the expressions of HIF-1α in local limb muscle and further accelerate the release of VEGF in the serum.