EPA + DHA supplementation reduces PMN activation in microenvironment of chronic venous leg ulcers: A randomized, double-blind, controlled study.

EPA + DHA supplementation reduces PMN activation in microenvironment of chronic venous leg ulcers: A randomized, double-blind, controlled study.
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DOI:
10.1111/wrr.12558
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发表时间:
2017-08
影响因子:
2.9
通讯作者:
Parinandi, Narasimham
Parinandi, Narasimham
中科院分区:
医学3区
文献类型:
--
作者:
McDaniel, Jodi C.;Szalacha, Laura;Sales, Michelle;Roy, Sashwati;Chafee, Scott;Parinandi, Narasimham

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慢性下肢静脉溃疡(CVLU)微环境中持续高水平的活化多形核白细胞(PMN)和PMN衍生的蛋白酶与慢性炎症和延迟愈合有关。不受控制的PMN活动最终会破坏新发育的组织并降解关键的生长因子。鱼油的生物活性成分(n-3二十碳五烯酸[EPA]和二十二碳六烯酸[DHA])具有很强的抗炎作用,并已被证明可以减轻PMN活性,但尚未在CVLU患者中进行测试。这项随机对照研究比较了口服EPA + DHA治疗与安慰剂减少CVLU微环境中PMN活化的有效性。在第0天、第28天和第56天,在接受标准压迫疗法和(1)EPA + DHA疗法(n = 16)或(2)安慰剂(n = 19)的患者的CVLU液中测量PMN(CD 15)和活化PMN(CD 66 b)的标志物以及PMN衍生的蛋白酶人中性粒细胞弹性蛋白酶和基质金属蛋白酶-8水平。到第56天,与第0天(p = 0.02)和第28天(p = 0.05)相比,EPA + DHA组CVLU液体中的CD 66 b+细胞百分比显著降低。重要的是,在EPA + DHA组中,基质金属蛋白酶-8和人中性粒细胞弹性蛋白酶的水平均随时间呈下降趋势,这也表明到第28天(减少57%)和第56天(减少76%)时伤口面积的减少大于对照组(分别为35%和59%)。此外,伤口面积的减少与第28天(p = 0.008)和第56天(p < 0.001)伤口液中的CD 15+细胞以及第28天(p = 0.04)和第56天(p = 0.009)的CD 66 b+细胞具有显著的负相关性。集体研究结果提供了补充证据,证明CVLU微环境中高水平的活化PMN抑制愈合,并表明EPA + DHA口服疗法可能调节PMN活性,并在添加到标准护理方案中时促进CVLU的愈合。
Sustained high levels of activated polymorphonuclear leukocytes (PMNs) and PMN-derived proteases in the microenvironment of chronic venous leg ulcers (CVLUs) are linked to chronic inflammation and delayed healing. Uncontrolled PMN activity eventually destroys newly developed tissue and degrades critical growth factors. The bioactive components of fish oil (n-3 eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have strong inflammation-resolving actions and have been shown to assuage PMN activity, but have not been tested in CVLU patients. This randomized controlled study compared the effectiveness of oral EPA + DHA therapy to a placebo for reducing PMN activation in CVLU microenvironments. At Days 0, 28, and 56, markers of PMNs (CD15) and activated PMNs (CD66b), and levels of PMN-derived proteases human neutrophil elastase and matrix metalloproteinase-8 were measured in CVLU fluid from patients receiving standard compression therapy and (1) EPA + DHA therapy (n = 16) or (2) placebo (n = 19). By Day 56, the EPA + DHA Group had a significantly lower percentage of CD66b+ cells in CVLU fluid compared to Day 0 (p = 0.02) and to Day 28 (p = 0.05). Importantly, there were downward trends in levels of both matrix metalloproteinase-8 and human neutrophil elastase over time in the EPA + DHA Group, which also demonstrated greater reductions in wound area by Day 28 (57% reduction) and Day 56 (76% reduction) than the Control Group (35% and 59%, respectively). Moreover, reductions in wound area had significant negative relationships with CD15+ cells in wound fluid at Days 28 (p = 0.008) and 56 (p < 0.001), and CD66b+ cells at Days 28 (p = 0.04) and 56 (p = 0.009). The collective findings provide supplemental evidence that high levels of activated PMNs in CVLU microenvironments inhibit healing, and suggest that EPA + DHA oral therapy may modulate PMN activity and facilitate healing of CVLUs when added to standard care regimens.
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