Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis
Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis
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DOI：
10.1016/j.matbio.2009.11.002
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发表时间：
2010-03-01
期刊：
影响因子：
6.9
通讯作者：
Wei, Guo
中科院分区：
文献类型：
--
作者：
Gao, Feng;Liu, Yiwen;Wei, Guo
透明质酸（HA）片段在血管生成加速中的生物学作用已被广泛研究。研究证实，HA寡糖（o-HA）能够在体外刺激新生血管，并在动物模型中促进血液流动或血管生成。然而，很少有实验室研究o-HA作为外源性治疗在体内损伤组织修复中的作用。由于其体积小，可能被周围组织迅速吸收，因此被认为在体内局部使用时可能失去活性。在这项研究中，我们制备了一种特殊的缓释凝胶，其中含有确定大小的o-HA混合物，并通过局部应用于急性伤口模型研究了o-HA的愈合效果。我们报道了o-HA复合物促进小鼠真皮切除伤口组织损伤的修复。将o-HA治疗与高分子量HA （HMW-HA）和已知的血管生成刺激剂VEGF进行比较。在治疗后6至8天，o-HA与对照组或HMW-HA组的伤口愈合率有显著差异，其中o-HA显示出伤口恢复的增加。组织学分析显示，o-HA处理后的损伤组织中新生血管和淋巴管的形成增加。此外，用o-HA处理伤口导致更多的肉芽生成、胶原沉积和成纤维细胞增殖。实时RT-PCR分析基因表达结果显示，o- ha处理的创面中部分细胞因子或粘附分子显著上调，与肉芽组织增多相对应。我们的研究结果表明，o-HA治疗可能在急性伤口修复中有用。(C) 2009年Elsevier B.V.出版
The biological roles of hyaluronan (HA) fragments in angiogenesis acceleration have been investigated recently. Studies have confirmed that oligosaccharides of HA (o-HA) are capable of stimulating neovascularization in vitro and promoting blood flow or angiogenesis in animal models. However, few laboratories have studied the function of o-HA as an exogenous treatment in injured tissue repair in vivo. It is thought that o-HA may lose its activities when used topically in vivo due to its small size, which may be absorbed quickly by the surrounding tissues. In this study, we prepared a special slow-releasing gel that contains a mixture of defined size of o-HA and studied the healing effects of o-HA by topical application to an acute wound model. We report that o-HA complex promotes the repair of tissue injury of a murine excisional dermal wound. The therapy by o-HA was compared with high molecular weight HA (HMW-HA) and the known angiogenesis stimulator, VEGF At days 6 to 8 after treatment, significant differences were seen in wound closure rates between o-HA and control or HMW-HA groups, in which o-HA showed an increased wound recovery. Histological analysis revealed that increased neo-blood and lymph vessels were formed in wounded tissues treated by o-HA. In addition, treatments of wounds with o-HA resulted in more granulation production, collagen deposition, and fibroblast proliferation. Analysis of gene expression by real-time RT-PCR demonstrated a significant up-regulation of some cytokines or adhesion molecules in o-HA-treated wounds, which corresponds with the increased granulation tissue in these wounds. Our findings suggested that o-HA therapy may be useful in acute Wound repair. (C) 2009 Published by Elsevier B.V.