Granulocyte colony-stimulating factor facilitates the angiogenesis induced by ultrasonic microbubble destruction
Granulocyte colony-stimulating factor facilitates the angiogenesis induced by ultrasonic microbubble destruction
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DOI：
10.1016/j.ultrasmedbio.2007.05.017
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发表时间：
2007-11-01
影响因子：
2.9
通讯作者：
Kohno, Masakazu
中科院分区：
文献类型：
--
作者：
Miyake, Yuichi;Ohmori, Koji;Kohno, Masakazu
超声波破坏微循环中的微泡（US/MB）会导致局部炎症细胞浸润，这已被证明可以诱导血管生成。粒细胞集落刺激因子 (G-CSF) 可动员骨髓中的粒单核细胞并增强这些细胞释放血管内皮生长因子 (VEGF)，也已应用于治疗性血管生成诱导。在本研究中，我们试图研究 G-CSF 预处理增强 US/MB 血管生成作用的潜力。小鼠缺血后肢用预先确定的最小有效剂量（300μg/kg）的G-CSF、单独的US/MB进行治疗，或者在股动脉去除后7天用G-CSF预处理然后进行US/MB治疗。静脉注射全氟化碳微泡后，使用诊断超声扫描仪在 1.4 MPa 峰值负压下以间歇脉冲局部声波对微泡进行超声破坏。治疗后 21 天，我们使用网格法量化表面血管分布，并使用碱性磷酸酶染色量化毛细血管密度。相对于正常肌肉中的毛细血管密度，治疗肢体中的毛细血管密度通过单独的 G-CSF 恢复至 74 +/- 13%，通过单独的 US/MB 恢复至 90 +/- 20%（与未治疗和单独的 G-CSF 相比，P < 0.05），并通过 G-CSF 预处理进一步增加至 101 +/- 21%。 G-CSF预处理和US/MB联合诱导的侧枝生长分别是单独G-CSF和单独US/MB诱导的生长的2.8倍和1.4倍（两者p<0.05）。因此，用单次最小有效剂量的 G-CSF 进行预处理可以增强 US/MB 的血管生成作用。 （电子邮件：komori@med.kakawa-u.ac.jp） (c) 2007 年世界超声医学与生物学联合会。
Ultrasonic destruction of microbubbles (US/MB) in the microcirculation causes local inflammatory cell infiltration, which has been shown to induce angiogenesis. Granulocyte colony-stimulating factor (G-CSF), which mobilizes myelomonocytic cells from the bone marrow and enhances vascular endothelial growth factor (VEGF) release from these cells, has also been applied to therapeutic angiogenesis induction. In the present study, we sought to examine the potential of G-CSF pretreatment to enhance the angiogenic effect of US/MB. Ischemic hindlimbs in mice were treated with either a predetermined minimal effective dose (300 mu g/kg) of G-CSF, US/MB alone or G-CSF pretreatment followed by US/MB at seven days after removal of the femoral artery. Ultrasonic destruction of microbubbles was performed as intermittent pulsed local insonation using a diagnostic ultrasound scanner at a peak negative pressure of 1.4 MPa after intravenous injection of perfluorocarbon microbubbles. At 21 days after the treatment, we quantified the surface vascularity using a grid method and the capillary density using an alkaline phosphatase stain. Relative to the capillary density in normal muscle, the capillary density in the treated limbs was restored to 74 +/- 13% by G-CSF alone and 90 +/- 20% by US/MB alone (P < 0.05 vs. both untreated and G-CSF alone), and further increased to 101 +/- 21% by G-CSF pretreatment. The collateral growth induced by the combination of G-CSF pretreatment and US/MB was 2.8- and 1.4-fold greater than the growth induced by G-CSF alone and US/MB alone, respectively (p < 0.05 for both). Thus, pretreatment with a single minimal effective dose of G-CSF can augment the angiogenic effect of US/MB. (E-mail: komori@med.kagawa-u.ac.jp) (c) 2007 World Federation for Ultrasound in Medicine & Biology.