背景:远端坏死和炎症是随机皮瓣存活(SFS)的两种最常见的健康后果。在各种研究中已经确定了亚精胺的抗炎作用。另一方面,考虑到一氧化氮分子参与亚精胺的作用方式以及其在皮肤组织功能中的作用,我们分析了亚精胺对SFS的可能影响,硝能途径和炎性细胞因子可能参与这些现象。
方法:每只大鼠用赋形剂(对照)或各种剂量的亚精胺(0.5、1、3、5、10和30mg/kg)预处理,然后进行随机模式皮瓣范例。此外,选择剂量为5mg/kg的亚精胺,一组大鼠在手术前20分钟接受亚精胺,并在手术后1天再接受一次亚精胺。然后,手术后7天,白细胞介素(IL)-6,肿瘤坏死因子(TNF)-α,干扰素-γ(IFN-γ),通过ELIZA试剂盒查询组织样品中的亚硝酸盐水平。通过DAPI染色和荧光显微镜评估血管内皮生长因子的表达。三种多胺的浓度,包括亚精胺,精胺,还有尸体,使用HPLC进行分析。
结果:在显微皮肤H&E染色分析中,用亚精胺5mg/kg预处理显著改善了SFS,并降低了坏死面积的百分比。此外,亚精胺通过调节一氧化氮和减少炎症细胞因子发挥了有希望的抗炎作用。
结论:亚精胺可以提高皮瓣的存活率,可能是通过硝化系统和炎症途径。这项临床前研究为亚精胺对大鼠SFS的潜在治疗作用提供了III级证据。基于动物模型的分析。需要进一步的研究来证实这些发现在临床环境中。
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BACKGROUND: Distal necrosis and inflammation are two of the most common health consequences of random-pattern skin flaps survival (SFS). Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the nitric oxide molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the SFS and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena.
METHODS: Each rat was pretreated with either a vehicle (control) or various doses of spermidine (0.5, 1, 3, 5, 10 and 30 mg/kg) and then was executed a random-pattern skin flap paradigm. Also, spermidine at the dose of 5 mg/kg was selected and one group rats received spermidine 20 min prior to surgery and one additional dose 1 day after operation. Then, 7 days after operations, interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), and nitrite levels were inquired in the tissue samples by ELIZA kit. Vascular endothelial growth factor expression was assessed by DAPI staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine, and cadaverine, were analyzed using HPLC.
RESULTS: Pretreatment with spermidine 5 mg/kg improved SFS considerably in microscopic skin H&E staining analysis and decreased the percentage of necrotic area. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of nitric oxide and reducing inflammatory cytokines.
CONCLUSIONS: Spermidine could improve skin flaps survival, probably through the nitrergic system and inflammation pathways. This preclinical study provides level III evidence for the potential therapeutic effects of spermidine on SFS in rats, based on the analysis of animal models. Further studies are needed to confirm these findings in clinical settings.
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