The elucidation of the mechanisms of cardiovascular hypertrophy and hyperplasia and the establishment of angiogenesis by therapeutic electrical stimulation

据报道，远低于肌肉收缩阈值的低电压电刺激(LVES)可以诱导血管内皮生长因子(VEGF)的合成。我们研究了LVES诱导大鼠后肢缺血模型中血管内皮生长因子的产生是由于缺氧还是炎症所致。我们还试图评估肝细胞生长因子(HGF)和成纤维细胞生长因子(FGF)等其他血管生成因子是否也参与了LVES的局部血管生成。第三，比较了LVES和高VES(High VES，HVEs)对血管生成因子的诱导作用，发现LVES不仅能显着增加组织中的血管生成因子，还能显着增加组织中HGF的表达。多克隆抗成纤维细胞生长因子抗体、抗IL 6抗体和缺氧诱导因子抗体在胫前肌的免疫组织化学染色水平与对照组无明显差异。间歇性LVES组的血管内皮细胞生长因子水平高于连续LVES组和间歇性LVES组，但差异无显着性。因此，在该模型中，不仅血管内皮生长因子参与了局部血管生成，而且肝细胞生长因子也参与了局部血管生成。实验还表明，在该模型中，LVES诱导的血管内皮生长因子的产生可能不是由于LVES的缺氧或炎症所致。第三，我们发现LVES诱导血管内皮生长因子生成的时间明显早于HVEs，并且在1d和5d之间，LVES刺激的VEGF合成与对照组的比率的增加小于HVEs。结论：在大鼠后肢缺血模型中，持续的LVES对VEGF和HGF的诱导是有效的，这在高压刺激下是不存在的，即使在低电压下，ES也可能对缺血性疾病有用。

Low voltage electrical stimulation (LVES) of skeletal muscle at a level far below the threshold of muscle contraction has been reported to induce synthesis of VEGF. We examined whether LVES induced VEGF production in hindlimb ischemia model of rats was due to hypoxia or inflammation. We also tried to evaluate whether other angiogenic factors, such as hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), also contribute to the local angiogenesis by LVES. Thirdly we compared the effect of LVES with that of high VES (HVES) on the induction of angiogenic factors.Not only VEGF but also HGF was significantly increased in tissues by LVES. There was no difference in the level of immunohistochemical staining of the tibialis anterior (TA) muscles with polyclonal anti FGF antibody, anti IL6 antibody, and HIF antibody between the LVES group and control group. The VEGF level of the intermittent HVES group tended to be higher than that of the continuous LVES or intermittent LVES groups although the difference was not significant. Therefore, not only VEGF but also HGF may contribute to the local angiogenesis by LVES in this model. It was also demonstrated that the LVES-induced VEGF production in this model may not be due to hypoxia or inflammation by LVES. Thirdly, we demonstrated that the induction of VEGF by LVES was seen at a significantly earlier period than that by HVES and that the increase in the ratio of VEGF synthesis of stimulated to control by LVES was smaller than that by HVES comparing between 1 day and 5 days.In conclusion, continuous LVES in a hindlimb ischemia model of rats was effective for VEGF and HGF induction which was not seen on high voltage stimulation, and ES might be useful for ischemic disease even at low voltage.