In vivo effect of hyperbaric oxygen on wound angiogenesis and epithelialization
In vivo effect of hyperbaric oxygen on wound angiogenesis and epithelialization
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DOI：
10.1111/j.1524-475x.2009.00455.x
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发表时间：
2009-03-01
影响因子：
2.9
通讯作者：
Frank, Johannes M.
中科院分区：
文献类型：
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作者：
Sander, Anna L.;Henrich, Dirk;Frank, Johannes M.
高压氧 (HBO) 疗法越来越多地应用于医疗实践的不同领域。虽然已被证明在多种情况下有效，但其作用机制尚不清楚。在本研究中，我们在体内无毛小鼠耳“受损”伤口模型中确定了 HBO 对伤口上皮化和新生血管形成的影响。为了损害伤口愈合，通过 iota-角叉菜胶预处理来消耗巨噬细胞。使用活体显微镜和计算机面积测量法测量伤口上皮化和新生血管形成。金属蛋白酶-2 (MMP-2)、MMP-9、金属蛋白酶-1 组织抑制剂在第 2 天和第 7 天，使用免疫组织化学测量了未受损愈合伤口中的上皮细胞形成和新生血管形成的速度，与未受损愈合伤口相比，受损伤口闭合时间显着延迟，HBO 治疗和巨噬细胞耗竭均未引起 MMP-2 表达的显着变化。相反，在接受 HBO 治疗的愈合受损组中，TNF-α、MMP-9 和 TIMP-1 显着上调。这些结果表明，HBO 治疗有效逆转了巨噬细胞减少对伤口上皮化和新生血管形成的负面影响，这种有益作用可能是由于刺激了 TNF-α 的产生，并且在较小程度上是由于金属蛋白酶的释放。
Hyperbaric oxygen (HBO) therapy is increasingly being used in different areas of medical practice. While demonstrated to be effective in several settings, its mechanism of action is not well understood. In the present study, we determined the effects of HBO on wound epithelialization and neovascularization in an in vivo hairless mouse ear "impaired'' wound model. To impair wound healing, macrophages were depleted by pretreatment with iota-carrageenan. Wound epithelialization and neovascularization were measured using intravital microscopy and computerized planimetry. Metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-alpha) were measured on days 2 and 7 using immunohistochemistry. In non-impaired healing wounds, the rate of epithelialization and neovascularization was significantly accelerated in the groups treated with HBO. Time to wound closure was significantly delayed in impaired compared with nonimpaired healing wounds and HBO treatment completely reversed this delay. Neither HBO treatment nor macrophage depletion caused significant alterations in MMP-2 expression in wounds. In contrast, TNF-alpha, MMP-9, and TIMP-1 were significantly up-regulated in the impaired healing group receiving HBO treatment. These results show that HBO therapy effectively reversed the negative effect exerted by macrophage reduction on wound epithelialization and neovascularization. This beneficial effect could be due to stimulation of TNF-alpha production and, to a lesser degree due to release of metalloproteinases.