Research of the therapeutic effect of low intensity pulsed ultrasound on pressure sore through the induction of angiogenesis by ultrasound exposure.

虽然超声用于治疗压疮，但几乎没有证据表明其在治疗压疮中的益处。因此，为了研究超声暴露在伤口愈合中的治疗证据，检测了低强度脉冲超声对人皮肤成纤维细胞中产生前列腺素E2（PGE 2）、碱性成纤维细胞生长因子（bFGF）、肝细胞生长因子（HGF）和血管内皮细胞生长因子（VEGF）的关键酶考克斯-1/2的mRNA诱导的影响。通过专门设计的装置将从皮肤样品获得的人真皮成纤维细胞暴露于低强度脉冲超声。酶联免疫吸附试验测定介质中PGE 2的释放。此外，从细胞中提取的mRNA被逆转录，并通过实时PCR测定来测量cDNA的量。低强度脉冲超声以时间依赖性方式增加真皮成纤维细胞的PGE 2释放。在考克斯-2 mRNA诱导下，30 mW/cm ^2超声照射1小时，PGE 2释放达到最大值1.24倍。此外，基本的bFGF，HGF和VEGF的mRNA诱导增强低强度脉冲超声暴露4小时。这些诱导被认为是独立的PGE 2释放的低强度脉冲超声曝光，因为考克斯-2选择性抑制剂，NS-398不能抑制这些诱导的血管生成因子的mRNA。因此，我们的研究结果确定了低强度脉冲超声的作用，以解释其可能增强皮肤溃疡愈合的潜在机制。需要进一步的研究来确定低强度脉冲超声在血管生成中的直接生物学相关性，这是组织发育和再生所必需的。

Though ultrasound is applied to the treatment of pressure sore, there was little evidence of benefit associated with the use of it in the treatment of pressure sore. Therefore, in order to investigate the therapeutic evidence of ultrasound exposure in the wound healing, the effect of low intensity pulsed-ultrasound on the mRNA induction of COX-1/2 which is the key enzyme for producing prostaglandin E2 (PGE2), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and vascular endothelial cell growth factor (VEGF) in human dermal fibroblasts was examined. Human dermal fibroblasts obtained from skin samples were exposed to a low intensity pulsed-ultrasound by specifically designed apparatus. An enzyme-linked immunosorbent assay determined the release of PGE2 in the medium. Also, mRNA extracted from the cells was reverse-transcribed and amount of cDNA was measured by real-time PCR assay. A low intensity pulsed-ultrasound increases the PGE2 release of dermal fibroblasts in a time-dependent fashion. PGE2 release by 30 mW/cm^2 ultrasound exposure reached maximum 1.24-fold at 1 hour with COX-2 mRNA induction. Also, mRNA induction of basic bFGF,HGF and VEGF were enhanced by a low intensity pulsed-ultrasound exposure for 4 hours. These inductions were supposed to be independent of the PGE2 release by a low intensity pulsed-ultrasound exposure because COX-2 selective inhibitor, NS-398 failed to suppress these inductions of mRNA of angiogenic factor. Thus, our results identify the effect of low intensity pulsed ultrasound to explain the potential mechanism by which it may augment the healing of skin ulcer. Further studies are required to ascertain the direct biological relevance of the low intensity pulsed-ultrasound in angiogenesis, which is required for the tissue development and regeneration.