Human beta-defensin-3 promotes wound heating in infected diabetic wounds
Human beta-defensin-3 promotes wound heating in infected diabetic wounds
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DOI：
10.1002/jgm.1287
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Eriksson, Elof
中科院分区：
文献类型：
--
作者：
Hirsch, Tobias;Spielmann, Malte;Eriksson, Elof
背景伤口感染是糖尿病患者的主要并发症。金黄色葡萄球菌是糖尿病伤口中最常见的单一分离株。人β-防御素（hBD）-3具有抗微生物活性，并且似乎在免疫应答中起关键作用。方法在约克郡猪背部建立切创模型，显微接种Ad 5-CMV-hBD-3载体。伤口接种S.结果hBD-3处理的伤口显示在第4天总细菌负荷为2.1 × 10（8）菌落形成单位（CFU）/g组织，而对照组为1.3 × 10（9）CFU/g组织（p < 0.001）。在第12天，未检测到统计学差异。上皮再形成显示表达hBD-3的伤口的75 +/-15%伤口闭合和对照的50 +/-16%（p < 0.01）。在第1-4天期间，hBD-3表达在15-20 ng/ml伤口液的范围内。低剂量的2 × 10（9）Ad 5-CMV-hBD-3对伤口愈合无影响，提示hBD-3具有剂量依赖性。金黄色葡萄球菌感染的糖尿病伤口的临床前大动物模型。此外，在第4天检测到细菌生长减少10倍。这些发现表明β防御素-3可能在糖尿病伤口愈合和伤口感染中起主要作用。版权所有（C）2008约翰威利父子有限公司
Background Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds.Methods Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation.Results hBD-3-treated wounds showed a total bacterial load of 2.1 X 10(8) colony-forming units (CFU)/g tissue, versus 1.3 x 10(9) CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 +/- 15% wound closure for hBD-3 expressing wounds and 50 +/- 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 x 10(9) Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3.Conclusions In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that betadefensin-3 may play a major role in diabetic wound healing and wound infections. Copyright (C) 2008 John Wiley & Sons, Ltd.