Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue infections
Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue infections
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DOI：
10.1111/j.1524-475x.2007.00239.x
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发表时间：
2007-05-01
影响因子：
2.9
通讯作者：
Ghahary, Aziz
中科院分区：
文献类型：
--
作者：
Ghaffari, Abdi;Jalili, Reza;Ghahary, Aziz
细菌负荷显著干扰慢性溃疡的愈合过程。一氧化氮(NO)在调节皮肤对感染的反应和伤口愈合方面起着关键作用。在以前的研究中，我们证明了外源NO气体(GNO)在百万分之200(Ppm)的情况下对一系列代表性病原体具有强大的抗菌作用。本研究的目的是探索GNO的体内抗菌特性，并测定皮肤细胞对GNO细胞毒作用的敏感性。在新西兰大白兔背部皮肤表面用金黄色葡萄球菌感染全层创面，用200ppm的GNO处理创面8h/d，连续3d，观察GNO的抗菌效果。在GNO存在的情况下，伤口细菌含量显著减少。在另一项单独的实验中，建立了人成纤维细胞、角质形成细胞和内皮细胞的原代培养，以测试GNO在皮肤中的细胞毒性。四甲基偶氮唑盐增殖试验表明，与细菌细胞不同，人皮肤细胞对GNO细胞毒性表现出显著的抵抗力。角质形成细胞和内皮细胞的体外迁移研究表明，GNO处理似乎不干扰伤口愈合过程中的再上皮化和血管生成。在GNO处理24小时后，成纤维细胞表达的前胶原水平显著增加，而基质金属蛋白酶-1mRNA的表达程度较小。总之，本研究为在不影响皮肤细胞活性和功能的情况下，将大剂量GNO作为抗菌药物用于治疗慢性无法愈合的溃疡或烧伤患者的感染提供了证据。
Bacterial burden significantly interferes with the healing process in chronic ulcers. Nitric oxide (NO) plays a key role in regulating skin's response to infection and wound healing. In previous studies, we demonstrated that exogenous NO gas (gNO) at 200 parts per million (ppm) exhibits potent antimicrobial effects against a representative range of pathogens. The aim of the present study is to explore the antimicrobial properties of gNO in vivo and to determine skin cells' sensitivity to the cytotoxic effects of gNO. To test gNO's antimicrobial effects, full-thickness wounds were infected with Staphylococcus aureus on the dorsal skin surface of New Zealand White rabbit and treated with 200 ppm gNO for 8 hours/day for 3 consecutive days. Significant reduction in wound bacterial content was observed in the presence of gNO. In a separate experiment, primary cultures of human fibroblasts, keratinocytes, and endothelial cells were established to test gNO's cytotoxicity in the skin. Methyl thiazolyl tetrazolium proliferation assays demonstrated that human skin cells, unlike bacterial cells, exhibited significant resistance toward gNO cytotoxicity. In vitro migration studies on keratinocytes and endothelial cells revealed that gNO treatment does not seem to interfere with reepithelialization and angiogenesis during the process of wound healing. Following 24 hours of gNO treatment, fibroblasts expressed significantly higher levels of procollagen and, to a lesser degree, a decrease in matrix metalloproteinase -1 mRNA. In conclusion, the present study provides evidence for the potential application of high doses of gNO as an antimicrobial agent for the treatment of infection in chronic nonhealing ulcers or burn patients, without compromising the viability, and function of skin cells.