Skin wound healing in the SKH-1 female mouse following inducible nitric oxide synthase inhibition
Skin wound healing in the SKH-1 female mouse following inducible nitric oxide synthase inhibition
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DOI：
10.1111/j.1365-2133.2007.08096.x
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发表时间：
2007-10-01
影响因子：
10.3
通讯作者：
Khan, N. K.
中科院分区：
文献类型：
--
作者：
Bell, R. R.;Dunstan, R. W.;Khan, N. K.
一氧化氮合酶（NOS）的诱导型亚型（iNOS）被炎症介质和/或其他病理应激上调，产生高水平的持续NO。累积数据表明NO在调节皮肤伤口愈合中的作用，尽管尚不清楚iNOS产生的NO和可能的内皮NOS（eNOS）在多大程度上有助于愈合过程。由于目前对iNOS在伤口愈合中的作用缺乏了解，以及缺乏可用于SC-842（一种iNOS抑制剂）的伤口愈合数据，因此进行了本体内研究以探讨SC-842在干扰伤口愈合中的可能作用。在无毛SKH-1小鼠中的缝合的切口伤口模型中，通过比较导致选择性抑制iNOS以及非选择性NOS抑制的各种剂量的iNOS抑制剂SC-842的体内作用（如通过导致eNOS和/或神经元NOS抑制的血压升高所证明的）来评价iNOS在伤口愈合过程中的作用。地塞米松被用作阳性control.Results伤口愈合在第28天postwounding，评估的拉伸强度和组织学，SC-842和车辆治疗的动物之间没有差异。与溶剂处理动物相比，在中剂量和高剂量处理动物的伤口中，在创伤后第14天观察到抗张强度降低，结论这些数据表明iNOS抑制对SKH中切口伤口的愈合没有不利影响。1只小鼠，通过伤口抗张强度和组织学评估28天。
Background The inducible isoform of the nitric oxide (NO) synthase (NOS) enzyme (iNOS) is upregulated by inflammatory mediators and/or other pathological stresses, generating high, sustained levels of NO. Cumulative data suggest a role for NO in the regulation of skin wound healing, although it is not clear to what extent NO generated by iNOS, and possibly endothelial NOS (eNOS), contribute to that healing process. Because of the current lack of understanding regarding the contribution of iNOS in wound healing, as well as the lack of wound healing data available for SC-842, an iNOS inhibitor, this in vivo study was conducted to investigate the possible role of SC-842 in interfering with wound healing.Objective This study evaluated whether inhibition of iNOS affects incisional skin wound healing.Methods Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, the role of iNOS in the wound healing process was evaluated by comparing in vivo effects of the iNOS inhibitor, SC-842, at various doses that result in selective inhibition of iNOS as well as nonselective NOS inhibition (as evidenced by elevated blood pressure resulting in inhibition of eNOS and/or neuronal NOS). Dexamethasone was used as a positive control.Results There were no differences in wound healing at day 28 postwounding, as evaluated by tensile strength and histology, between SC-842- and vehicle-treated animals. A decrease in tensile strength was noted at day 14 postwounding in wounds from the mid- and high-dose-treated animals as compared with vehicle-treated animals, but this difference was slight and was not associated with histological differences from vehicle-treated controls.Conclusion These data indicate that iNOS inhibition does not adversely affect the healing of incisional wounds in SKH-1 mice as assessed over 28 days by wound tensile strength and histology.