Potential application of gaseous nitric oxide as a topical antimicrobial agent
Potential application of gaseous nitric oxide as a topical antimicrobial agent
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DOI：
10.1016/j.niox.2005.08.003
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发表时间：
2006-02-01
影响因子：
3.9
通讯作者：
Ghahary, A
中科院分区：
文献类型：
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作者：
Ghaffari, A;Miller, CC;Ghahary, A
在不愈合的伤口和烧伤中细菌定植的存在显著干扰正常的愈合过程。最近的证据表明，一氧化氮（NO）在宿主防御感染和调节伤口愈合和血管生成中起重要作用。我们研究了医用级气态形式的NO（gNO）作为一种新型抗菌剂在伤口感染中的潜在应用。使用连续水平流动递送系统，在体外测试gNO对一系列病原体的抗菌活性，包括金黄色葡萄球菌的临床分离株、耐甲氧西林的S.金黄色葡萄球菌、大肠杆菌、B族链球菌、铜绿假单胞菌和白色念珠菌。为探讨局部应用gNO对人皮肤的影响，分别采用H-3-TdR掺入法和北方印迹法检测了体外培养的人皮肤成纤维细胞增殖和细胞外基质基因表达的变化。在200 ppm gNO下观察到有效的杀菌活性，平均4.1 +/- 1.1 h完全停止细菌生长。有趣的是，该剂量的gNO对暴露长达48小时的培养物中的人真皮成纤维细胞没有显示出任何细胞毒性作用。成纤维细胞中的基因转录分析显示，MMP-1 mRNA表达的显着增加，早在暴露于gNO后2小时。虽然程度较低，但在相同的成纤维细胞中也观察到I型前胶原的显著减少。这项研究的结果表明，外源性气态NO具有有效的显着抗菌特性，可以有利于减少烧伤或不愈合溃疡感染伤口的细菌负荷。(c)2005年爱思唯尔公司All rights reserved.
The presence of bacterial colonization in non-healing Wounds and burn injuries interferes significantly with the normal process of healing. Recent evidence suggests that nitric oxide (NO) plays an important role in host defense against infection and regulates wound healing and angiogenesis. We investigated the potential application of a medical-grade gaseous form of NO (gNO) as a novel antibacterial agent in wound infection. Using a continuous horizontal-flow delivery system, the antibacterial activity of gNO was tested in vitro against a range of pathogens, including clinical isolates of Staplylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Group B Streptococcus, Pseudomonas aeruginosa, and Candida albicans. To probe the effect of topical application of gNO on the human skin, the proliferation and extracellular matrix gene expression of human dermal fibroblasts in culture were also analyzed by H-3-thymidine incorporation assay and Northern blot techniques, respectively. Potent bacteriocidal activity was observed at 200 ppm gNO with an average of 4.1 +/- 1.1 h to completely stop bacterial growth. Interestingly, this dose of gNO did not show any cytotoxic effect ill human dermal fibroblasts in culture exposed for up to 48 h. Analysis of gene transcription in fibroblasts revealed a significant increase in MMP-1 mRNA expression as early as 2h post-exposure to gNO. Although to a lesser degree, a significant reduction in type I procollagen was also observed in the same fibroblasts. The results of this study suggest that exogenous gaseous NO has potent significant antibacterial properties that can be beneficial in reducing bacterial burden in infected wound in burn injuries or non-healing ulcers. (c) 2005 Elsevier Inc. All rights reserved.